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  Subjects -> CHEMISTRY (Total: 898 journals)
    - ANALYTICAL CHEMISTRY (55 journals)
    - CHEMISTRY (632 journals)
    - CRYSTALLOGRAPHY (21 journals)
    - ELECTROCHEMISTRY (28 journals)
    - INORGANIC CHEMISTRY (43 journals)
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    - PHYSICAL CHEMISTRY (71 journals)

CHEMISTRY (632 journals)                  1 2 3 4 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 14)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 28)
ACS Catalysis     Hybrid Journal   (Followers: 46)
ACS Chemical Neuroscience     Hybrid Journal   (Followers: 22)
ACS Combinatorial Science     Hybrid Journal   (Followers: 23)
ACS Macro Letters     Hybrid Journal   (Followers: 27)
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 42)
ACS Nano     Hybrid Journal   (Followers: 309)
ACS Photonics     Hybrid Journal   (Followers: 14)
ACS Symposium Series     Full-text available via subscription  
ACS Synthetic Biology     Hybrid Journal   (Followers: 25)
Acta Chemica Iasi     Open Access   (Followers: 5)
Acta Chimica Slovaca     Open Access   (Followers: 2)
Acta Chimica Slovenica     Open Access   (Followers: 1)
Acta Chromatographica     Full-text available via subscription   (Followers: 8)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7)
Acta Scientifica Naturalis     Open Access   (Followers: 3)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Adsorption Science & Technology     Open Access   (Followers: 6)
Advanced Functional Materials     Hybrid Journal   (Followers: 60)
Advanced Science Focus     Free   (Followers: 5)
Advances in Chemical Engineering and Science     Open Access   (Followers: 75)
Advances in Chemical Science     Open Access   (Followers: 19)
Advances in Chemistry     Open Access   (Followers: 24)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19)
Advances in Drug Research     Full-text available via subscription   (Followers: 25)
Advances in Environmental Chemistry     Open Access   (Followers: 7)
Advances in Enzyme Research     Open Access   (Followers: 10)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 12)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 27)
Advances in Nanoparticles     Open Access   (Followers: 15)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Polymer Science     Hybrid Journal   (Followers: 45)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 3)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 8)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Al-Kimia : Jurnal Penelitian Sains Kimia     Open Access  
Alchemy : Journal of Chemistry     Open Access   (Followers: 3)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 68)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 22)
American Journal of Chemistry     Open Access   (Followers: 32)
American Journal of Plant Physiology     Open Access   (Followers: 13)
American Mineralogist     Hybrid Journal   (Followers: 16)
Anadolu University Journal of Science and Technology A : Applied Sciences and Engineering     Open Access  
Analyst     Full-text available via subscription   (Followers: 37)
Angewandte Chemie     Hybrid Journal   (Followers: 181)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 259)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 4)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 9)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 13)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 2)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 9)
Applied Spectroscopy     Full-text available via subscription   (Followers: 26)
Applied Surface Science     Hybrid Journal   (Followers: 34)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 3)
Asian Journal of Chemistry and Pharmaceutical Sciences     Open Access  
Atomization and Sprays     Full-text available via subscription   (Followers: 4)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 3)
Avances en Quimica     Open Access  
Biochemical Pharmacology     Hybrid Journal   (Followers: 11)
Biochemistry     Hybrid Journal   (Followers: 379)
Biochemistry Insights     Open Access   (Followers: 6)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 11)
Bioinspired Materials     Open Access   (Followers: 5)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 2)
Biomacromolecules     Hybrid Journal   (Followers: 23)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 5)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 138)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 90)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 1)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 11)
Canadian Mineralogist     Full-text available via subscription   (Followers: 6)
Carbohydrate Research     Hybrid Journal   (Followers: 25)
Carbon     Hybrid Journal   (Followers: 70)
Catalysis for Sustainable Energy     Open Access   (Followers: 8)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 7)
Catalysis Science and Technology     Free   (Followers: 8)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 12)
Cellulose     Hybrid Journal   (Followers: 10)
Cereal Chemistry     Full-text available via subscription   (Followers: 5)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 21)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 75)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 27)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
Chemical Reviews     Hybrid Journal   (Followers: 205)
Chemical Science     Open Access   (Followers: 28)
Chemical Technology     Open Access   (Followers: 34)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 57)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 23)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 7)
Chemistry & Biology     Full-text available via subscription   (Followers: 33)
Chemistry & Industry     Hybrid Journal   (Followers: 8)
Chemistry - A European Journal     Hybrid Journal   (Followers: 168)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 16)
Chemistry and Materials Research     Open Access   (Followers: 21)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Open Access   (Followers: 3)
Chemistry Letters     Full-text available via subscription   (Followers: 45)
Chemistry of Materials     Hybrid Journal   (Followers: 267)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 20)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 1)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 3)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 12)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 11)
Chromatographia     Hybrid Journal   (Followers: 22)
Chromatography     Open Access   (Followers: 2)
Chromatography Research International     Open Access   (Followers: 6)
Cogent Chemistry     Open Access   (Followers: 2)
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 11)
Colloids and Interfaces     Open Access  
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 7)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 24)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Communications Chemistry     Open Access  
Composite Interfaces     Hybrid Journal   (Followers: 7)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 1)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 10)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 4)
Copernican Letters     Open Access   (Followers: 1)
Corrosion Series     Full-text available via subscription   (Followers: 7)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 8)
Croatica Chemica Acta     Open Access  
Crystal Structure Theory and Applications     Open Access   (Followers: 4)
CrystEngComm     Full-text available via subscription   (Followers: 13)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Chromatography     Hybrid Journal  
Current Green Chemistry     Hybrid Journal   (Followers: 1)
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Microwave Chemistry     Hybrid Journal  
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 14)
Current Research in Chemistry     Open Access   (Followers: 9)
Current Science     Open Access   (Followers: 73)
Current Trends in Biotechnology and Chemical Research     Open Access   (Followers: 2)
Dalton Transactions     Full-text available via subscription   (Followers: 23)
Detection     Open Access   (Followers: 4)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)

        1 2 3 4 | Last

Journal Cover
Advances in Protein Chemistry and Structural Biology
Journal Prestige (SJR): 0.791
Citation Impact (citeScore): 2
Number of Followers: 20  
 
  Full-text available via subscription Subscription journal
ISSN (Online) 1876-1623
Published by Elsevier Homepage  [3157 journals]
  • Intracellular signaling of the AMP-activated protein kinase
    • Abstract: Publication date: Available online 14 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Miribane Dërmaku-Sopjani, Mentor Sopjani AMP-activated protein kinase (AMPK) is an essential cellular energy sensor that senses the cellular energy status and maintains cellular energy balance. The AMPK coordinates cellular and whole-body energy homeostasis through stimulating catabolic ATP-producing and suppressing anabolic ATP-consuming intracellular signaling pathways. AMPK induces autophagy and inhibits cell growth in response to starvation, a process that involves regulating certain intracellular signaling molecules. Recent advances demonstrated the AMPK to exert tumor suppressor activity realized through various signaling molecules by stimulating different cellular processes such as apoptosis, autophagy and cell growth and proliferation. AMPK can also be used to protect against metabolic syndrome. AMPK has previously been reported to be either directly or indirectly involved in the regulation of many different cellular transport proteins of high importance for cellular physiology and pathophysiology. Thus, AMPK provides a necessary link between cellular energy metabolism and cellular transport activities. A better understanding of the AMPK role in intracellular signaling under physiological and pathological conditions may represent a potential strategy for developing therapies for treating many different human diseases and disorders, in which AMPK plays a key role.
       
  • Elucidating the role of interacting residues of the MSH2-MSH6 complex in
           DNA repair mechanism: A computational approach
    • Abstract: Publication date: Available online 7 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): D. Thirumal Kumar, B. Susmita, E. Judith, J. Priyadharshini Christy, C. George Priya Doss, Hatem Zayed The DNA repair system is crucial to repair the error resulting in DNA replication. MSH2-MSH6 protein complex plays a significant role in maintaining the mismatch repair mechanism. Mutations in the interface between the two proteins compromise their function in the repair process. The present study aims to understand the impact of missense mutations in the interacting sites of the MSH2-MSH6 protein complex. MSH6 is unstable due to the disordered N-terminal domain. This is stabilized by the MSH2 hetero-dimerization. We used pathogenicity and stability predictors to identify the missense mutations that could be more pathogenic with the destabilizing property. The mutations W764C of MSH2, and L1201F and G1316E of MSH6 were predicted to be highly deleterious and destabilizing by all the in silico predictors. The dynamic motion of the native and mutant (W764C) MSH2-MSH6 protein complexes was further investigated using Molecular Dynamics Simulations of the GROMACS package. The Root Mean Square Deviation (RMSD), Radius of Gyration (Rg), and change in a number of intramolecular hydrogen bonds (H-bonds) were analyzed using the embedded packages of GROMACS. From the simulation studies, we observed higher deviation, lower protein compactness, and a decrease in the number of intramolecular hydrogen bonds in the mutant W764C MSH2-MSH6 protein complex. The observed results from the computational methods suggest the involvement of higher structural impact on the MSH2-MSH6 protein complex upon W764C mutation could affect the DNA repair mechanism.
       
  • A computational model to predict the structural and functional
           consequences of missense mutations in O6-methylguanine DNA
           methyltransferase
    • Abstract: Publication date: Available online 7 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): D. Thirumal Kumar, Enid Mendonca, J. Priyadharshini Christy, C. George Priya Doss, Hatem Zayed DNA repair mechanism is a process through which the cell repairs its damaged DNA. Although there are several mechanisms involved in the DNA repair mechanisms, the direct reversal method is the simplest and does not require a reference template, in which the guanine bases are often methylated, and the methyl guanine methyl transferase protein (MGMT) reverses them. The mutations occurring in the MGMT protein might result in dysfunction of such DNA repair mechanism. In this study, we attempted to evaluate the impact of six missense mutations (Y114E, Y114A, R128G, R128A, R128K, and C145A) at three active-site positions (Y114, C145, and R128) as this might hinder the DNA binding to the protein. These six mutations were subjected to pathogenicity, stability, and conservation analysis using online servers such as PredictSNP, iStable, and ConSurf, respectively. From the predictions, all the six mutations were almost predicted to be significant. Considering true positives, true negatives, false positives, and false negatives, three mutations (Y114E, R128G, and C145A) showed “loss of DNA repair activity,” and were analyzed further using molecular dynamics simulations (MDS) using GROMACS for 50 ns. MDS run showed that the C145A mutant demonstrated higher structural deviation, decreased compactness, and the binding patterns. The Y114E mutant showed almost a null effect from the structural analysis. Finally, the R128G mutant showed structural variations in between the C145A and Y114E mutations of MGMT protein. We believe that the observed findings in this computational approach might further pave a way of providing better treatment measures by understanding the DNA repair mechanisms.
       
  • Aquaporin water channels: New perspectives on the potential role in
           inflammation
    • Abstract: Publication date: Available online 5 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Margherita Sisto, Domenico Ribatti, Sabrina Lisi Aquaporins (AQPs) are a family of membrane water channel proteins that osmotically modulate water fluid homeostasis in several tissues; some of them also transport small solutes such as glycerol. At the cellular level, the AQPs regulate not only cell migration and transepithelial fluid transport across membranes, but also common events that are crucial for the inflammatory response. Emerging data reveal a new function of AQPs in the inflammatory process, as demonstrated by their dysregulation in a wide range of inflammatory diseases including edematous states, cancer, obesity, wound healing and several autoimmune diseases. This chapter summarizes the discoveries made so far about the structure and functions of the AQPs and provides updated information on the underlying mechanisms of AQPs in several human inflammatory diseases. The discovery of new functions for AQPs opens new vistas offering promise for the discovery of mechanisms and therapeutic opportunities in inflammatory disorders.
       
  • Mechanistic link between DNA damage sensing, repairing and signaling
           factors and immune signaling
    • Abstract: Publication date: Available online 3 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Shibani Mukherjee, Salim Abdisalaam, Souparno Bhattacharya, Kalayarasan Srinivasan, Debapriya Sinha, Aroumougame Asaithamby Previously, DNA damage sensing, repairing and signaling machineries were thought to mainly suppress genomic instability in response to genotoxic stress. Emerging evidence indicates a crosstalk between DNA repair machinery and the immune system. In this chapter, we attempt to decipher the molecular choreography of how factors, including ATM, BRCA1, DNA-PK, FANCA/D2, MRE11, MUS81, NBS1, RAD51 and TREX1, of multiple DNA metabolic processes are directly or indirectly involved in suppressing cytosolic DNA sensing pathway-mediated immune signaling. We provide systematic details showing how different DDR factors’ roles in modulating immune signaling are not direct, but are rather a consequence of their inherent ability to sense, repair and signal in response to DNA damage. Unexpectedly, most DDR factors negatively impact the immune system; that is, the immune system shows defective signaling if there are defects in DNA repair pathways. Thus, in addition to their known DNA repair and replication functions, DDR factors help prevent erroneous activation of immune signaling. A more precise understanding of the mechanisms by which different DDR factors function in immune signaling can be exploited to redirect the immune system for both preventing and treating autoimmunity, cellular senescence and cancer in humans.
       
  • Recent advances in computational studies of GPCR-G protein interactions
    • Abstract: Publication date: Available online 3 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Jinan Wang, Yinglong Miao Protein-protein interactions are key in cellular signaling. G protein-coupled receptors (GPCRs), the largest superfamily of human membrane proteins, are able to transduce extracellular signals (e.g., hormones and neurotransmitters) to intracellular proteins, in particular the G proteins. Since GPCRs serve as primary targets of ~ 1/3 of currently marketed drugs, it is important to understand mechanisms of GPCR signaling in order to design selective and potent drug molecules. This chapter focuses on recent advances in computational studies of the GPCR-G protein interactions using bioinformatics, protein-protein docking and molecular dynamics simulation approaches.
       
  • Replication stress: Driver and therapeutic target in genomically instable
           cancers
    • Abstract: Publication date: Available online 28 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Pepijn M. Schoonen, Sergi Guerrero Llobet, Marcel A.T.M. van Vugt Genomically instable cancers are characterized by progressive loss and gain of chromosomal fragments, and the acquisition of complex genomic rearrangements. Such cancers, including triple-negative breast cancers and high-grade serous ovarian cancers, typically show aggressive behavior and lack actionable driver oncogenes. Increasingly, oncogene-induced replication stress or defective replication fork maintenance is considered an important driver of genomic instability. Paradoxically, while replication stress causes chromosomal instability and thereby promotes cancer development, it intrinsically poses a threat to cellular viability. Apparently, tumor cells harboring high levels of replication stress have evolved ways to cope with replication stress. As a consequence, therapeutic targeting of such compensatory mechanisms is likely to preferentially target cancers with high levels of replication stress and may prove useful in potentiating chemotherapeutic approaches that exert their effects by interfering with DNA replication. Here, we discuss how replication stress drives chromosomal instability, and the cell cycle-regulated mechanisms that cancer cells employ to deal with replication stress. Importantly, we discuss how mechanisms involving DNA structure-specific resolvases, cell cycle checkpoint kinases and mitotic processing of replication intermediates offer possibilities in developing treatments for difficult-to-treat genomically instable cancers.
       
  • Relationship between mitofusin 2 and cancer
    • Abstract: Publication date: Available online 27 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): A. Allegra, V. Innao, A.G. Allegra, C. Musolino Mitochondria are dynamic organelles whose actions are fundamental for cell viability. Within the cell, the mitochondrial system is incessantly modified via the balance between fusion and fission processes. Among other proteins, mitofusin 2 is a central protagonist in all these mitochondrial events (fusion, trafficking, contacts with other organelles), the balance of which causes the correct mitochondrial action, shape, and distribution within the cell. Here we examine the structural and functional characteristics of mitofusin 2, underlining its essential role in numerous intracellular pathways, as well as in the pathogenesis of cancer.
       
  • Activating mutations of the gp130/JAK/STAT pathway in human diseases
    • Abstract: Publication date: Available online 27 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Juliane Lokau, Christoph Garbers Cytokines of the interleukin-6 (IL-6) family are involved in numerous physiological and pathophysiological processes. Dysregulated and increased activities of its members can be found in practically all human inflammatory diseases including cancer. All cytokines activate several intracellular signaling cascades, including the Jak/STAT, MAPK, PI3K, and Src/YAP signaling pathways. Additionally, several mutations in proteins involved in these signaling cascades have been identified in human patients, which render these proteins constitutively active and result in a hyperactivation of the signaling pathway. Interestingly, some of these mutations are associated with or even causative for distinct human diseases, making them interesting targets for therapy. This chapter describes the basic biology of the gp130/Jak/STAT pathway, summarizes what is known about the molecular mechanisms of the activating mutations, and gives an outlook how this knowledge can be exploited for targeted therapy in human diseases.
       
  • DNA repair by photolyases
    • Abstract: Publication date: Available online 20 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Ibrahim Halil Kavakli, Nuri Ozturk, Seref Gul Photolyases belong to the cryptochrome/photolyase protein family (CPF) which perform different functions such as DNA repair, circadian photoreceptor, and transcriptional regulation. Photolyase is a flavoprotein that repairs UV-induced DNA damages of cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6-4) photoproducts using blue-light as an energy source. This enzyme has two chromophores: flavin adenine dinucleotide (FAD) as a cofactor and a photoantenna such as methenyltetrahydrofolate (MTHF). The FAD is essential for catalysis of the DNA repair. The second chromophore absorbs photons from the blue light spectrum and transfers energy to FAD to increase the repair efficiency of the enzyme. Phylogenetic analysis in which amino acid sequences of several hundreds of CPF members are used suggests that they form more classes than we have considered so far. In this chapter, we discussed structure-functions and reaction mechanisms of different classes of photolyases.
       
  • Intracellular protein complexes involved in synapse assembly in
           presynaptic neurons
    • Abstract: Publication date: Available online 20 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Kyung Ah Han, Ji Won Um, Jaewon Ko The presynaptic active zone, composed of evolutionarily conserved protein complexes, is a specialized area that serves to orchestrate precise and efficient neurotransmitter release by organizing various presynaptic proteins involved in mediating docking and priming of synaptic vesicles, recruiting voltage-gated calcium channels, and modulating presynaptic nerve terminals with aligned postsynaptic structures. Among membrane proteins localized to active zone, presynaptic neurexins and LAR-RPTPs (leukocyte common antigen-related receptor tyrosine phosphatase) have emerged as hubs that orchestrate both shared and distinct extracellular synaptic adhesion pathways. In this chapter, we discuss intracellular signaling cascades involved in recruiting various intracellular proteins at both excitatory and inhibitory synaptic sites. In particular, we highlight recent studies on key active zone proteins that physically and functionally link these cascades with neurexins and LAR-RPTPs in both vertebrate and invertebrate model systems. These studies allow us to build a general, universal view of how presynaptic active zones operate together with postsynaptic structures in neural circuits.
       
  • Chromatin control in double strand break repair
    • Abstract: Publication date: Available online 20 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Anastas Gospodinov, Iva Ugrinova DNA double strand breaks (DSB) are the most deleterious type of damage inflicted on DNA by various environmental factors and as consequences of normal cellular metabolism. The multistep nature of DSB repair and the need to assemble large protein complexes at repair sites necessitate multiple chromatin changes there. This review focuses on the key findings of how chromatin regulators exert temporal and spatial control on DSB repair. These mechanisms coordinate repair with cell cycle progression, lead to DSB repair pathway choice, provide accessibility of repair machinery to damaged sites and move the lesions to nuclear environments permissive for repair.
       
  • The roles of cytosolic quality control proteins, SGTA and the BAG6
           complex, in disease
    • Abstract: Publication date: Available online 18 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Rashi Benarroch, Jennifer M. Austin, Fahmeda Ahmed, Rivka L. Isaacson SGTA is a co-chaperone that, in collaboration with the complex of BAG6/UBL4A/TRC35, facilitates the biogenesis and quality control of hydrophobic proteins, protecting them from the aqueous cytosolic environment. This work includes targeting tail-anchored proteins to their resident membranes, sorting of membrane and secretory proteins that mislocalize to the cytoplasm and endoplasmic reticulum-associated degradation of misfolded proteins. Since these functions are all vital for the cell's continued proteostasis, their disruption poses a threat to the cell, with a particular risk of protein aggregation, a phenomenon that underpins many diseases. Although the specific disease implications of machinery involved in quality control of hydrophobic substrates are poorly understood, here we summarize much of the available information on this topic.
       
  • Computational and modeling approaches to understand the impact of the
           Fabry's disease causing mutation (D92Y) on the interaction with
           pharmacological chaperone 1-deoxygalactonojirimycin (DGJ)
    • Abstract: Publication date: Available online 18 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): D. Thirumal Kumar, E. Judith, J. Priya dharshini Christy, R. Siva, Iftikhar Aslam Tayubi, Chiranjib Chakraborty, C. George Priya Doss, Hatem Zayed Fabry's disease (FD) is the second most commonly occurring lysosomal storage disorders (LSDs). The mutations in GLA protein were widely found to be causative for the Fabry's disease. These mutations result in alternate splicing methods that affect the stability and function of the protein. The mutations near the active site of the protein results in protein misfolding. In this study, we have retrieved the missense mutation data from the three public databases (NCBI, UniProt, and HGMD). We used multiple in silico tools to predict the pathogenicity and stability of these mutations. Mutations in the active sites (D92Y, C142Y, D170V, and D266N) of the protein were screened for the phenotyping analysis using SNPeffect 4.0. Mutant D92Y was predicted to increase the amyloid propensity as well as severely reduce the protein stability and the remaining mutations showed no significant results by SNPeffect 4.0. Protein dynamics simulations (PDS) were performed to understand the behavior of the proteins due to the mutations. The simulation results showed that the D92Y mutant was more severe (higher deviation, loss of intramolecular hydrogen bonds, and lower compactness) than the other protein mutants (C142Y, D170V, and D266N). Further, the action of pharmacological chaperone 1-deoxygalactonojirimycin (DGJ) over the severe mutation was studied using the molecular docking analysis. Chaperone DGJ, an iminosugar plays a convincing role in repairing the misfolded protein and helps the protein to achieve its normal function. From the molecular docking analysis, we observed that both the native protein and protein with D92Y mutation followed similar interaction patterns. Further, the docked complexes (native-DGJ and mutant-DGJ) were subjected to PDS analysis. From the simulation analysis, we observed that DGJ had shown the better effect on the protein with the D92Y mutation. This elucidates that DGJ can still be used as a promising chaperone to treat the FD caused by mutations of GLA protein.
       
  • When safeguarding goes wrong: Impact of oxidative stress on protein
           homeostasis in health and neurodegenerative disorders
    • Abstract: Publication date: Available online 18 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Ravit Mesika, Dana Reichmann Cellular redox status is an established player in many different cellular functions. The buildup of oxidants within the cell is tightly regulated to maintain a balance between the positive and negative outcomes of cellular oxidants. Proteins are highly sensitive to oxidation, since modification can cause widespread unfolding and the formation of toxic aggregates. In response, cells have developed highly regulated systems that contribute to the maintenance of both the global redox status and protein homeostasis at large. Changes to these systems have been found to correlate with aging and age-related disorders, such as neurodegenerative pathologies. This raises intriguing questions as to the source of the imbalance in the redox and protein homeostasis systems, their interconnectivity, and their role in disease progression.Here we focus on the crosstalk between the redox and protein homeostasis systems in neurodegenerative diseases, specifically in Alzheimer's, Parkinson's, and ALS. We elaborate on some of the main players of the stress response systems, including the master regulators of oxidative stress and the heat shock response, Nrf2 and Hsf1, which are essential features of protein folding, and mediators of protein turnover. We illustrate the elegant mechanisms used by these components to provide an immediate response, including protein plasticity controlled by redox-sensing cysteines and the recruitment of naive proteins to the redox homeostasis array that act as chaperons in an ATP-independent manner.
       
  • Claspin: From replication stress and DNA damage responses to cancer
           therapy
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Diana Azenha, Maria Celeste Lopes, Teresa C. Martins Cancer is still one of the major causes of death worldwide. Radiation therapy and chemotherapy remain the main treatment modalities in cancer. These therapies exert their effect mainly through interference with DNA replication and induction of DNA damage. It is believed that one way of improving the efficacy of cancer treatment will be to inhibit the replication stress and DNA damage responses and promote mitotic catastrophe of cancer cells. So far, the majority of the efforts have focused central players of checkpoint responses, such as ATR and CHK1, and DNA damage repair, such as PARPs. Being a key player in the replication stress response, checkpoint activation, and the DNA damage response, Claspin constitutes an attractive therapeutic target in cancer, namely for radio- and chemo-sensitization. In this review, we will go through Claspin functions in the replication stress and DNA damage responses and will discuss how Claspin can be targeted in cancer treatment, as well as the effects of Claspin inhibition.
       
  • Controlling the balance between chromosome break repair pathways
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Sonia Jimeno, Fernando Mejías-Navarro, Rosario Prados-Carvajal, Pablo Huertas Broken chromosomes are among the most complex and more difficult to repair DNA lesions. The loss of the continuity of the DNA molecule presents a challenge to the cells, thus the repair of DNA double strand breaks might lead to genomic alterations. Indeed, to minimize this threat to genomic integrity, different DNA repair pathways can act on a broken chromosome. The balance between them is tightly controlled, and it heavily depends on global and local cellular cues. In this chapter, we review our current understanding on the repair of DNA double strand breaks and focus in the regulation of the balance between alternative pathways. Most of this modulation takes place at the level of DNA end resection. Here, we focus mostly on the local signals that control the repair pathway choice, as the global cues have been extensively reviewed recently. We described epigenetic marks that either facilitate or inhibit DNA resection and homologous recombination, from histone marks and chromatin remodelers to non-coding RNA and RNA-related factors.
       
  • cAMP-mediated regulation of melanocyte genomic instability: A
           melanoma-preventive strategy
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Nathaniel C. Holcomb, Robert-Marlo Bautista, Stuart G. Jarrett, Katharine M. Carter, Madeline Krentz Gober, John A. D’Orazio Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage. There is now ample evidence that suggests that the melanocortin 1 receptor (MC1R) is a major melanoma risk factor. Inherited loss-of-function mutations in MC1R are common in melanoma-prone persons, correlating with a less melanized skin complexion and poorer recovery from mutagenic photodamage. We and others are interested in the MC1R signaling pathway in melanocytes, its mechanisms of enhancing genomic stability and pharmacologic opportunities to reduce melanoma risk based on those insights. In this chapter, we review melanoma risk factors, the MC1R signaling pathway, and the relationship between MC1R signaling and DNA repair.
       
  • Targeting DNA repair in precision medicine
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Reena Beggs, Eddy S. Yang Precision medicine is an emerging treatment paradigm that aims to find the right therapy at the right time based on an individual's unique genetic background, environment, and lifestyle. One area of precision medicine that has had success is targeting DNA repair in cancer. DNA is exposed to constant stress and there are repair mechanisms in place to maintain genetic integrity. These repair mechanisms can be targeted as a treatment strategy. In this chapter, we will focus on current efforts to target DNA repair pathways as part of precision oncology-based treatments.
       
  • Functional principles and regulation of molecular chaperones
    • Abstract: Publication date: Available online 1 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Vinay Dahiya, Johannes Buchner To be able to perform their biological function, a protein needs to be correctly folded into its three dimensional structure. The protein folding process is spontaneous and does not require the input of energy. However, in the crowded cellular environment where there is high risk of inter-molecular interactions that may lead to protein molecules sticking to each other, hence forming aggregates, protein folding is assisted. Cells have evolved robust machinery called molecular chaperones to deal with the protein folding problem and to maintain proteins in their functional state. Molecular chaperones promote efficient folding of newly synthesized proteins, prevent their aggregation and ensure protein homeostasis in cells. There are different classes of molecular chaperones functioning in a complex interplay. In this review, we discuss the principal characteristics of different classes of molecular chaperones, their structure-function relationships, their mode of regulation and their involvement in human disorders.
       
  • A comparative computational approach toward pharmacological chaperones
           (NN-DNJ and ambroxol) on N370S and L444P mutations causing Gaucher's
           disease
    • Abstract: Publication date: Available online 1 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): D. Thirumal Kumar, Sharada Iyer, J. Priyadharshini Christy, R. Siva, Iftikhar Aslam Tayubi, C. George Priya Doss, Hatem Zayed Gaucher's disease (GD) is the most commonly known lysosomal disorder that occurs due to mutations in the β-glucocerebrosidase (GBA) protein. Our previous findings (Thirumal Kumar, Eldous, Mahgoub, George Priya Doss, Zayed, 2018) and other reports concluded that the mutations N370S and L444P are the most significant mutations that could cause disruptions in protein stability and structure. These disruptions lead to protein misfolding and result in a diseased condition. Enzyme Replacement Therapy (ERT) and Pharmacological chaperone therapy (PCT) are currently used to treat GD caused by mutations in the GBA protein. The extreme disparity in cost between ERT and chaperone therapy, shifted the attention toward chaperone therapy. The most common chaperones in the market and trial phases to treat GD are Isofagomine, Miglustat, Eliglustat, NN-DNJ, and Ambroxol. In the era of personalized medicine, it is often necessary to understand the drug likeliness of each chaperone. In this context, the present study utilized molecular docking analysis to understand the interaction behavior of the chaperone toward the native and the two mutants N370S and L444P. The molecular dynamics simulation analyses performed on chaperones (NN-DNJ and Ambroxol) interaction showed that the chaperone NN-DNJ possesses better affinity toward the protein with N370S mutation whereas chaperone Ambroxol showed better activity against both the significant mutations (N370S and L444P). This study is expected to serve as a platform for drug repurposing.
       
  • Protein stability and degradation in health and disease
    • Abstract: Publication date: Available online 28 November 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Lene Clausen, Amanda B. Abildgaard, Sarah K. Gersing, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen The cellular proteome performs highly varied functions to sustain life. Since most of these functions require proteins to fold properly, they can be impaired by mutations that affect protein structure, leading to diseases such as Alzheimer's disease, cystic fibrosis, and Lynch syndrome. The cell has evolved an intricate protein quality control (PQC) system that includes degradation pathways and a multitude of molecular chaperones and co-chaperones, all working together to catalyze the refolding or removal of aberrant proteins. Thus, the PQC system limits the harmful consequences of dysfunctional proteins, including those arising from disease-causing mutations. This complex system is still not fully understood. In particular the structural and sequence motifs that, when exposed, trigger degradation of misfolded proteins are currently under investigation. Moreover, several attempts are being made to activate or inhibit parts of the PQC system as a treatment for diseases. Here, we briefly review the present knowledge on the PQC system and list current strategies that are employed to exploit the system in disease treatment.
       
  • Inflammatory response and its relation to sphingolipid metabolism
           proteins: Chaperones as potential indirect anti-inflammatory agents
    • Abstract: Publication date: Available online 28 November 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Z. Begum Yagci, Elif Esvap, Hatice Asuman Ozkara, Kutlu O. Ulgen, Elif Ozkirimli Lysosome is the organelle responsible for breaking down macromolecules to maintain homeostasis and to fight infection. The disruption of normal lysosomal function due to mutations in the sphingolipid metabolism proteins leads to a class of lysosomal storage diseases (LSDs). Defective autophagy and activation of inflammation are observed in most LSDs. The crosstalk between these key metabolic pathways suggests that therapeutic approaches used in the treatment of LSDs may provide anti-inflammatory therapies against chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease. Here, we review the role of sphingolipids in the inflammatory response and build a protein-protein interaction network for proteins related with sphingolipid metabolism and inflammation to identify key interaction partners for the crosstalk between sphingolipids and inflammation. In addition, we present an overview of LSDs in relation with sphingolipids and inflammation, and review the pharmacological chaperones identified for these diseases.
       
  • Structural and functional insights on the roles of molecular chaperones in
           the mistargeting and aggregation phenotypes associated with primary
           hyperoxaluria type I
    • Abstract: Publication date: Available online 28 November 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): José Ángel Fernández-Higuero, Isabel Betancor-Fernández, Noel Mesa-Torres, Arturo Muga, Eduardo Salido, Angel L. Pey To carry out their biological function in cells, proteins must be folded and targeted to the appropriate subcellular location. These processes are controlled by a vast collection of interacting proteins collectively known as the protein homeostasis network, in which molecular chaperones play a prominent role. Protein homeostasis can be impaired by inherited mutations leading to genetic diseases. In this chapter, we focus on a particular disease, primary hyperoxaluria type 1 (PH1), in which disease-associated mutations exacerbate protein aggregation in the cell and mistarget the peroxisomal alanine:glyoxylate aminotransferase (AGT) protein to mitochondria, in part due to native state destabilization and enhanced interaction with Hsp60, 70 and 90 chaperone systems. After a general introduction of molecular chaperones and PH1, we review our current knowledge on the structural and energetic features of PH1-causing mutants that lead to these particular pathogenic mechanisms. From this perspective, and in the context of the key role of molecular chaperones in PH1 pathogenesis, we present and discuss current and future perspectives for pharmacological treatments for this disease.
       
  • Chaperones and retinal disorders
    • Abstract: Publication date: Available online 28 November 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Maxim Sokolov, Ravi P. Yadav, Celine Brooks, Nikolai O. Artemyev Defects in protein folding and trafficking are a common cause of photoreceptor degeneration, causing blindness. Photoreceptor cells present an unusual challenge to the protein folding and transport machinery due to the high rate of protein synthesis, trafficking and the renewal of the outer segment, a primary cilium that has been modified into a specialized light-sensing compartment. Phototransduction components, such as rhodopsin and cGMP-phosphodiesterase, and multimeric ciliary transport complexes, such as the BBSome, are hotspots for mutations that disrupt proteostasis and lead to the death of photoreceptors. In this chapter, we review recent studies that advance our understanding of the chaperone and transport machinery of phototransduction proteins.
       
  • Combined Quantum Mechanics and Molecular Mechanics Studies of Enzymatic
           Reaction Mechanisms
    • Abstract: Publication date: Available online 13 August 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Jon Ainsley, Alessio Lodola, Adrian J. Mulholland, Christo Z. Christov, Tatyana G. Karabencheva-Christova The combined quantum mechanics/molecular mechanics (QM/MM) methods have become a valuable tool in computational biochemistry and received versatile applications for studying the reaction mechanisms of enzymes. The approach combines the calculations of the electronic structure of the active site by QM, with modeling of the protein environment using MM force field, which allows the long-range electrostatics and steric effects on the enzyme reactivity to be accounted for. In this review, we review some key theoretical and computational aspects of the method and we also present some applications to particular enzymatic reactions such as tryptophan-7-halogenase, cyclooxygenase-1, and the epidermal growth factor receptor.
       
  • Computational Methods for Efficient Sampling of Protein Landscapes and
           Disclosing Allosteric Regions
    • Abstract: Publication date: Available online 25 July 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Canan Atilgan Methods developed toward computational exploration of protein landscapes have become standardized tools to assess biophysical experimental findings. They are also used on their own right to discover the workings of the protein as a molecular machine, potential sites of interest for protein functioning, allosteric regions in proteins, and communication pathways between different sites on a protein. With the development of reliable force fields that describe interactions in biomolecules, molecular dynamics (MD) simulations have become the prime tool for this purpose. While it is now straightforward to carry out MD simulations up to microseconds with current computers readily available to researchers, many processes of biological interest occur on several of orders of magnitudes slower timescales. Thus, the latter problems are attackable through MD by a handful of researchers that have access to the most powerful computers. Alternatively, physics-based methods to interrogate the protein energy landscape are in continuous development to circumvent this problem. In addition to opening the routes for advancement to a large number of researchers that have access to modest computational resources, they have the advantage of providing an understanding of the mechanisms that govern protein dynamics. Here we discuss network-based approaches geared toward understanding protein dynamics. These include (i) construction of residue networks which view proteins as networks of nodes connected through local interactions and (ii) construction of proteins as elastic networks whose modes of motion may be manipulated to achieve allowed conformational changes. Limitations of the methods as well as opportunities for future exploitation are described.
       
  • The OECD Principles for (Q)SAR Models in the Context of Knowledge
           Discovery in Databases (KDD)
    • Abstract: Publication date: Available online 4 May 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Gabriela Gomez-Jimenez, Karla Gonzalez-Ponce, Durbis J. Castillo-Pazos, Abraham Madariaga-Mazon, Joaquin Barroso-Flores, Fernando Cortes-Guzman, Karina Martinez-Mayorga The steps followed in the knowledge discovery in databases (KDD) process are well documented and are widely used in different areas where exploration of data is used for decision making. In turn, while different workflows for developing quantitative structure–activity relationship (QSAR) models have been proposed, including combinatorial use of QSAR, there is now agreement on common requirements for building trustable predictive models. In this work, we analyze and confront the steps involved in KDD and QSAR and present how they comply with the OECD principles for the validation, for regulatory purposes, of QSAR models.
       
  • Computational Methods to Discover Compounds for the Treatment of Chagas
           Disease
    • Abstract: Publication date: Available online 16 March 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Eduardo M. Cortés-Ruiz, Oscar Palomino-Hernández, Karla Daniela Rodríguez-Hernández, Bertha Espinoza, José L. Medina-Franco Infectious diseases continue to be a major public health. Among these diseases, American trypanosomiasis or Chagas disease (CD) is a major cause of morbidity and death for millions of people in Latin America. The two drugs currently available for the treatment of CD have poor efficacy and major side effects. Thus, there is a pressing need to develop safe and effective drugs against this disease. Herein we review the diversity and coverage of chemical space of compounds tested as inhibitors of Trypanosoma cruzi, a parasite causing CD. We also review major molecular targets currently pursued to kill the parasite and recent computational approaches to identify inhibitors for such targets.
       
  • Computational Methods for Epigenetic Drug Discovery: A Focus on Activity
           Landscape Modeling
    • Abstract: Publication date: Available online 5 March 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): J. Jesús Naveja, C. Iluhí Oviedo-Osornio, José L. Medina-Franco Epigenetic drug discovery is an emerging strategy against several chronic and complex diseases. The increased interest in epigenetics has boosted the development and maintenance of large information on structure–epigenetic activity relationships for several epigenetic targets. In turn, such large databases—many in the public domain—are a rich source of information to explore their structure–activity relationships (SARs). Herein, we conducted a large-scale analysis of the SAR of epigenetic targets using the concept of activity landscape modeling. A comprehensive quantitative analysis and a novel visual representation of the epigenetic activity landscape enabled the rapid identification of regions of targets with continuous and discontinuous SAR. This information led to the identification of epigenetic targets for which it is anticipated an easier or a more difficult drug-discovery program using conventional hit-to-lead approaches. The insights of this work also enabled the identification of specific structural changes associated with a large shift in biological activity. To the best of our knowledge, this work represents the largest comprehensive SAR analysis of several epigenetic targets and contributes to the better understanding of the epigenetic activity landscape.
       
 
 
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