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
Protein Conformational Dynamics
Protein Conformational Dynamics - 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 Conformational Dynamics write by Ke-li Han. This book was released on 2014-01-20. Protein Conformational Dynamics available in PDF, EPUB and Kindle. This book discusses how biological molecules exert their function and regulate biological processes, with a clear focus on how conformational dynamics of proteins are critical in this respect. In the last decade, the advancements in computational biology, nuclear magnetic resonance including paramagnetic relaxation enhancement, and fluorescence-based ensemble/single-molecule techniques have shown that biological molecules (proteins, DNAs and RNAs) fluctuate under equilibrium conditions. The conformational and energetic spaces that these fluctuations explore likely contain active conformations that are critical for their function. More interestingly, these fluctuations can respond actively to external cues, which introduces layers of tight regulation on the biological processes that they dictate. A growing number of studies have suggested that conformational dynamics of proteins govern their role in regulating biological functions, examples of this regulation can be found in signal transduction, molecular recognition, apoptosis, protein / ion / other molecules translocation and gene expression. On the experimental side, the technical advances have offered deep insights into the conformational motions of a number of proteins. These studies greatly enrich our knowledge of the interplay between structure and function. On the theoretical side, novel approaches and detailed computational simulations have provided powerful tools in the study of enzyme catalysis, protein / drug design, protein / ion / other molecule translocation and protein folding/aggregation, to name but a few. This work contains detailed information, not only on the conformational motions of biological systems, but also on the potential governing forces of conformational dynamics (transient interactions, chemical and physical origins, thermodynamic properties). New developments in computational simulations will greatly enhance our understanding of how these molecules function in various biological events.
Protein Dynamics, Function, and Design
Protein Dynamics, Function, and 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 Protein Dynamics, Function, and Design write by Oleg Jardetzky. This book was released on 2012-12-06. Protein Dynamics, Function, and Design available in PDF, EPUB and Kindle. This volume is a collection of articles from the proceedings of the International School of Structural Biology and Magnetic Resonance 3rd Course: Protein Dynamics, Function, and Design. This NATO Advance Study Institute was held in Erice at the Ettore Majorana Centre for Scientific Culture on April 16-28, 1997. The aim of the Institute was to bring together experts applyipg different physical methods to problems of macro molecular dynamics-notably x-ray diffraction, NMR and other forms of spectroscopy, and molecular dynamics simulations. Emphasis was placed on those systems and types of problems-such as mechanisms of allosteric control, signal transmission, induced fit to different ligands with its implications for drug design, and the effects of dynamics on structure determination-where a correlation of findings obtained by different methods could shed the most light on the mechanisms involved and stimulate the search for new approaches. The individual articles represent the state of the art in each of the areas cov ered and provide a guide to the original literature in this rapidly developing field. v CONTENTS 1. Determining Structures of ProteinlDN A Complexes by NMR Angela M. Gronenbom and G. Marius Clore 2. Fitting Protein Structures to Experimental Data: Lessons from before Your Mother Was Born . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Jeffrey C. Hoch, Alan S. Stem, and Peter J. Connolly 3. Multisubunit Allosteric Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 William N. Lipscomb 4. Studying Protein Structure and Function by Directed Evolution: Examples with Engineered Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Andreas Pliickthun 5. High Pressure Effects on Protein Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Understanding Protein Dynamics, Binding and Allostery for Drug Design
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.
Intrinsically Disordered Proteins
Intrinsically Disordered Proteins - 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 Intrinsically Disordered Proteins write by Nicola Salvi. This book was released on 2019-06-14. Intrinsically Disordered Proteins available in PDF, EPUB and Kindle. Intrinsically Disordered Proteins: Dynamics, Binding, and Function thoroughly examines and ties together the fundamental biochemical functions of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs), including signaling, binding, and regulation, with the methodology for study and the associated pathways for drug design and therapeutic intervention. The role of new mechanistic, computational, and experimental approaches in IDP study are explored in depth, with methods for the characterization of IDP dynamics; models, simulations, and mechanisms of IDP and IDR binding; and biological and medical implications of IDP dynamics prominently featured. Written and edited by leading scientists in the field, this book explores groundbreaking areas such as ensemble descriptions of IDPs and IDRs, single-molecule studies of IDPs and IDRs, IDPs and IDRs in membraneless organelles, and molecular mechanisms of fibrillation of IDPs. Intrinsically Disordered Proteins provides students and researchers in biochemistry, molecular biology, and applied microbiology with a comprehensive and updated discussion of the complex dynamics of IDPs and IDRs. Provides in-depth discussion of fundamental IDP and IDR dynamics, function, and binding, with mechanistic insight to support new drug development Describes the role of new computational and experimental approaches in characterizing the binding of IDPs to their functional targets Features chapter contributions from international experts in IDP and IDR biochemical function and methods of study
