Understanding Protein Dynamics, Binding and Allostery for Drug Design - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Understanding Protein Dynamics, Binding and Allostery for Drug Design write by Guang Hu. This book was released on 2021-06-08. Understanding Protein Dynamics, Binding and Allostery for Drug Design available in PDF, EPUB and Kindle.
Protein Allostery in Drug Discovery
Protein Allostery in Drug Discovery - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Protein Allostery in Drug Discovery write by Jian Zhang. This book was released on 2019-11-09. Protein Allostery in Drug Discovery available in PDF, EPUB and Kindle. The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery—as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc.
The Use of Protein Dynamics in the Study of Protein Conformational Transition and Functionality and Its Relevance in Drug Design
The Use of Protein Dynamics in the Study of Protein Conformational Transition and Functionality and Its Relevance in Drug Design - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook The Use of Protein Dynamics in the Study of Protein Conformational Transition and Functionality and Its Relevance in Drug Design write by JoAnne Jean Babula. This book was released on 2020. The Use of Protein Dynamics in the Study of Protein Conformational Transition and Functionality and Its Relevance in Drug Design available in PDF, EPUB and Kindle. Misregulation of protein signaling pathways is the basis for many human diseases, and thus 95% of Food and Drug Administration approved drugs target proteins. Proteins are dynamic entities which can undergo transitions to reach different conformational states. The conformational state of a protein, or its three-dimensional shape, is intricately linked to functions, such as association with endogenous or exogenous binding partners, or catalysis. Thus, it is of interest to the pharmacological community to understand the mechanisms of protein conformational state transitions in order to better target and control protein functions. In two case studies, I show the importance of understanding protein dynamics in protein function and drug design. In the case of human immunodeficiency virus-1 (HIV-1) protease, a tremendous "open-and-closed" conformational transition is revealed by Molecular Dynamics Simulations (MDS). Through observing the dramatic difference in effectiveness of two Darunavir inhibitor derivatives differentiated by a single atom at locking the protease in the closed conformation, we discovered the residues and mechanism that lead to the protease's conformational transition. This mechanism also explained the significant difference in the binding conformation and binding affinity of these two inhibitors. This study provides insight on how to improve the potency and anti-viral capacity of these compounds. In the second case study, MDS enabled us to observe the conformational transitions of a family of seven isoforms known as the 14-3-3 proteins. Many vital cellular processes involve all or select 14-3-3 isoforms, making this family very difficult to target. Through MDS, I discovered different conformational samplings among these 14-3-3 isoforms which were then validated by SAXS. Subsequently, a FRET-based ligand binding assay was developed which can screen for preferential 14-3-3 isoform binding of endogenous ligands, giving hope that using conformations unique to a 14-3-3 isoform of interest can provide a method for selective drug design
Allosterism in Drug Discovery
Allosterism in Drug Discovery - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Allosterism in Drug Discovery write by Dario Doller. This book was released on 2016-11-24. Allosterism in Drug Discovery available in PDF, EPUB and Kindle. Although the concept of allosterism has been known for over half a century, its application in drug discovery has exploded in recent years. The emergence of novel technologies that enable molecular-level ligand-receptor interactions to be studied in studied in unprecedented detail has driven this trend. This book, written by the leaders in this young research area, describes the latest developments in allosterism for drug discovery. Bringing together research in a diverse range of scientific disciplines, Allosterism in Drug Discovery is a key reference for academics and industrialists interested in understanding allosteric interactions. The book provides an in-depth review of research using small molecules as chemical probes and drug candidates that interact allosterically with proteins of relevance to life sciences and human disease. Knowledge of these interactions can then be applied in the discovery of the novel therapeutics of the future. This book will be useful for people working in all disciplines associated with drug discovery in academia or industry, as well as postgraduate students who may be working in the design of allosteric modulators.
FREE ENERGY SIMULATIONS AND STRUCTURAL STUDIES OF PROTEIN-LIGAND BINDING AND ALLOSTERY
FREE ENERGY SIMULATIONS AND STRUCTURAL STUDIES OF PROTEIN-LIGAND BINDING AND ALLOSTERY - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook FREE ENERGY SIMULATIONS AND STRUCTURAL STUDIES OF PROTEIN-LIGAND BINDING AND ALLOSTERY write by Peng He. This book was released on 2018. FREE ENERGY SIMULATIONS AND STRUCTURAL STUDIES OF PROTEIN-LIGAND BINDING AND ALLOSTERY available in PDF, EPUB and Kindle. Protein-ligand binding and protein allostery play a crucial role in cell signaling, cell regulation, and modern drug discovery. In recent years, experimental studies of protein structures including crystallography, NMR, and Cryo-EM are widely used to investigate the functional and inhibitory properties of a protein. On the one hand, structural classification and feature identification of the structures of protein kinases, HIV proteins, and other extensively studied proteins would have an increasingly important role in depicting the general figures of the conformational landscape of those proteins. On the other hand, free energy calculations which include the conformational and binding free energy calculation, which provides the thermodynamics basis of protein allostery and inhibitor binding, have proven its ability to guide new inhibitor discovery and protein functional studies. In this dissertation, I have used multiple different analysis and free energy methods to understand the significance of the conformational and binding free energy landscapes of protein kinases and other disease-related proteins and developed a novel alchemical-based free energy method, restrain free energy release (R-FEP-R) to overcome the difficulties in choosing appropriate collective variables and pathways in conformational free energy methods like umbrella sampling and metadynamics.
