Simulating Enzyme Reactivity Computational Methods In Enzyme Catalysis

Author : Inaki Tunon
Publisher : Royal Society of Chemistry
ISBN 13 : 1782624295
Total Pages : 558 pages
Book Rating : 4.95/5 ( download)

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Download or read book Simulating Enzyme Reactivity written by Inaki Tunon and published by Royal Society of Chemistry. This book was released on 2016-11-25 with total page 558 pages. Available in PDF, EPUB and Kindle. Book excerpt: Exploring the theories, methodologies and applications in simulations of enzymatic reactions, this book is a great resource for postgraduate students and researchers.

Author : John Maclane
Publisher : Createspace Independent Publishing Platform
ISBN 13 : 9781548041595
Total Pages : 446 pages
Book Rating : 4.99/5 ( download)

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Download or read book Simulating Enzyme Reactivity Computational Methods in Enzyme Catalysis written by John Maclane and published by Createspace Independent Publishing Platform. This book was released on 2017-06-07 with total page 446 pages. Available in PDF, EPUB and Kindle. Book excerpt: The simulation of enzymatic processes is a well-established field within computational chemistry, as demonstrated by the 2013 Nobel Prize in Chemistry. It has been attracting increasing attention in recent years due to the potential applications in the development of new drugs or new environmental-friendly catalysts. Featuring contributions from renowned authors, including Nobel Laureate Arieh Warshel, this book explores the theories, methodologies and applications in simulations of enzyme reactions. It is the first book offering a comprehensive perspective of the field by examining several different methodological approaches and discussing their applicability and limitations. The book provides the basic knowledge for postgraduate students and researchers in chemistry, biochemistry and biophysics, who want a deeper understanding of complex biological process at the molecular level.

Author : Inaki Tunon
Publisher : Royal Society of Chemistry
ISBN 13 : 1782626832
Total Pages : 558 pages
Book Rating : 4.31/5 ( download)

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Download or read book Simulating Enzyme Reactivity written by Inaki Tunon and published by Royal Society of Chemistry. This book was released on 2016-11-16 with total page 558 pages. Available in PDF, EPUB and Kindle. Book excerpt: The simulation of enzymatic processes is a well-established field within computational chemistry, as demonstrated by the 2013 Nobel Prize in Chemistry. It has been attracting increasing attention in recent years due to the potential applications in the development of new drugs or new environmental-friendly catalysts. Featuring contributions from renowned authors, including Nobel Laureate Arieh Warshel, this book explores the theories, methodologies and applications in simulations of enzyme reactions. It is the first book offering a comprehensive perspective of the field by examining several different methodological approaches and discussing their applicability and limitations. The book provides the basic knowledge for postgraduate students and researchers in chemistry, biochemistry and biophysics, who want a deeper understanding of complex biological process at the molecular level.

Author : Vicent Moliner
Publisher : Frontiers Media SA
ISBN 13 : 2889632725
Total Pages : 173 pages
Book Rating : 4.25/5 ( download)

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Download or read book Challenges in Computational Enzymology written by Vicent Moliner and published by Frontiers Media SA. This book was released on 2019-12-31 with total page 173 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author : Vasanthanathan Poongavanam
Publisher : John Wiley & Sons
ISBN 13 : 3527840737
Total Pages : 882 pages
Book Rating : 4.31/5 ( download)

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Download or read book Computational Drug Discovery written by Vasanthanathan Poongavanam and published by John Wiley & Sons. This book was released on 2024-01-19 with total page 882 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Drug Discovery A comprehensive resource that explains a wide array of computational technologies and methods driving innovation in drug discovery Computational Drug Discovery: Methods and Applications (2 volume set) covers a wide range of cutting-edge computational technologies and computational chemistry methods that are transforming drug discovery. The book delves into recent advances, particularly focusing on artificial intelligence (AI) and its application for protein structure prediction, AI-enabled virtual screening, and generative modeling for compound design. Additionally, it covers key technological advancements in computing such as quantum and cloud computing that are driving innovations in drug discovery. Furthermore, dedicated chapters that addresses the recent trends in the field of computer aided drug design, including ultra-large-scale virtual screening for hit identification, computational strategies for designing new therapeutic modalities like PROTACs and covalent inhibitors that target residues beyond cysteine are also presented. To offer the most up-to-date information on computational methods utilized in computational drug discovery, it covers chapters highlighting the use of molecular dynamics and other related methods, application of QM and QM/MM methods in computational drug design, and techniques for navigating and visualizing the chemical space, as well as leveraging big data to drive drug discovery efforts. The book is thoughtfully organized into eight thematic sections, each focusing on a specific computational method or technology applied to drug discovery. Authored by renowned experts from academia, pharmaceutical industry, and major drug discovery software providers, it offers an overview of the latest advances in computational drug discovery. Key topics covered in the book include: Application of molecular dynamics simulations and related approaches in drug discovery The application of QM, hybrid approaches such as QM/MM, and fragment molecular orbital framework for understanding protein-ligand interactions Adoption of artificial intelligence in pre-clinical drug discovery, encompassing protein structure prediction, generative modeling for de novo design, and virtual screening. Techniques for navigating and visualizing the chemical space, along with harnessing big data to drive drug discovery efforts. Methods for performing ultra-large-scale virtual screening for hit identification. Computational strategies for designing new therapeutic models, including PROTACs and molecular glues. In silico ADMET approaches for predicting a variety of pharmacokinetic and physicochemical endpoints. The role of computing technologies like quantum computing and cloud computing in accelerating drug discovery This book will provide readers an overview of the latest advancements in computational drug discovery and serve as a valuable resource for professionals engaged in drug discovery.

Author : Dennis R. Salahub
Publisher : Royal Society of Chemistry
ISBN 13 : 1839164670
Total Pages : 411 pages
Book Rating : 4.75/5 ( download)

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Download or read book Multiscale Dynamics Simulations written by Dennis R. Salahub and published by Royal Society of Chemistry. This book was released on 2021-09-24 with total page 411 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past decade, great strides have been taken in developing methodologies that can treat more and more complex nano- and nano-bio systems embedded in complex environments. Multiscale Dynamics Simulations covers methods including DFT/MM-MD, DFTB and semi-empirical QM/MM-MD, DFT/MMPOL as well as Machine-learning approaches to all of the above. Focusing on key methodological breakthroughs in the field, this book provides newcomers with a comprehensive menu of multiscale modelling options so that they can better chart their course in the nano/bio world.

Author : Dennis R. Salahub
Publisher : Royal Society of Chemistry
ISBN 13 : 1839161787
Total Pages : 411 pages
Book Rating : 4.80/5 ( download)

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Download or read book Multiscale Dynamics Simulations: Nano and Nano-bio Systems in Complex Environments written by Dennis R. Salahub and published by Royal Society of Chemistry. This book was released on 2021-10-01 with total page 411 pages. Available in PDF, EPUB and Kindle. Book excerpt: Focusing on key methodological breakthroughs in the field, this book provides newcomers with a comprehensive menu of multiscale modelling options.

Author : Dongda Zhang
Publisher : Royal Society of Chemistry
ISBN 13 : 1839165634
Total Pages : 441 pages
Book Rating : 4.34/5 ( download)

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Download or read book Machine Learning and Hybrid Modelling for Reaction Engineering written by Dongda Zhang and published by Royal Society of Chemistry. This book was released on 2023-12-20 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author : Song Yang
Publisher :
ISBN 13 :
Total Pages : 214 pages
Book Rating : 4.63/5 ( download)

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Download or read book Computational Study of Enzymes and Molecular Machines written by Song Yang and published by . This book was released on 2018 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chapters 1-6 describe studies of enzymes and their applications in biocatalysis. Biocatalysis, the use of natural enzymes or engineered enzymes to produce molecules of interest, has been an emerging and favorable approach to supplement or replace traditional organic synthesis. Enzymes are very efficient and selective in catalysis, and enzyme catalysis is also environmentally friendly. The first portion of this dissertation reports the theoretical study of several enzymes that catalyze very different reactions, including oxidation, halogenation as well as Diels-Alder reactions. The study reveals the mechanism behind each enzyme-catalyzed reaction in terms of efficiency, substrate specificity and regio-/stereo selectivity. In addition to the understanding of each enzyme, mutations are proposed based on the mechanism of the enzyme reactions to improve the natural enzymes for better catalysis. Chapter 1 introduces a general strategy for synthesis of macrolactones using nickel catalyzed C-C coupling and a site-selective P450 C-H oxidations carried out at Michigan by the groups of Montgomery and Sherman. Quantum mechanical (QM) computations show the intrinsic energy barriers at different hydrogen atoms at different sites in a single substrate. Molecular dynamic (MD) simulations reproduce the site selectivity and stereoselectivity in the biocatalytic oxidations with the aid of QM results. Our results suggest the linker length and its interaction with the enzyme determines the reaction yield. Chapter 2 presents a study of the first natural Diels-Alderase (DAase) and its mechanism for catalyzing a DA reaction. QM calculations suggest the reaction goes through an ambimodal TS leading to both [4+2] and [6+4] adducts. MD simulations show that trajectories pass through the TS and go to [4+2] adduct more in the enzyme than in gas phase or water. The enzyme influences the outcome of bifurcation dramatically, mainly through hydrophobic contact. The energy barrier of the enzymatic reaction is also reproduced accurately with our newly developed method: Environment Perturbed TS Sampling (EPTSS). Chapter 3 studies the Cope rearrangement and cyclization in hapalindole biogenesis. The X-ray crystal structure of HpiC1 is reported in this study. Mutagenesis study as well as computational computations uncover the key residues for the enzymatic reaction. QM computations show the reaction goes through an acid-catalyzed [3,3]-sigmatropic rearrangement. The switch from hapalindole to fischerindole is explained by the position change of the terminal electrophilic aromatic substitution in MD simulations. Chapter 4 describes the mechanism of Diels-Alderase PyrI4 in pyrroindomycins biosynthesis. Density functional theory (DFT) calculations and EPTSS calculations compare the energy barriers of the reaction in the gas phase, theozyme model, and in the enzyme. Hydrogen bonding has limited contribution to the TS stabilization in the enzyme. MD simulations show that hydrophobic interactions dominate in the catalysis of the enzyme catalyzed Diels-Alder reaction by fitting with the exo TS better than other TSs or the reactants. Chapter 5 presents the study of a multifunctional P450 MycG and its substrate specificity. QM computations reveal the mechanism behind the MycG biopathway. MD simulations show that a hydrophobic cavity in MycG differentiates the three different substrates favors the binding of the natural substrate. Based on MD simulations, potential beneficial mutations are proposed and tested by the Sherman group at Michigan, and are proven to improve the enzyme performance in experiment. Chapter 6 studies flavin dependent halogenase and its regioselectivity in directed evolution. The flavin dependent halogenase RebH was engineered to catalyze chlorination at different regioselective sites of tryptamine. QM calculations reveal that the intrinsic energy barriers at different sites are similar to each other. Docking and MD simulations show the different binding poses are favorable in WT and the mutants. Key mutations are identified through MD simulations and reverse mutations. Chapters 7-9 are projects about molecular machines in solid state as well as solvent phase, studied experimentally by the Garcia-Garibay group. Ever since Prof. Feynman's famous talk "There is plenty of room at the bottom", nanotechnology has witnessed tremendous progress in the synthesis and design of molecular machines capable of mechanical movements. The early stage of molecular machine development was simply to mimic macroscopic designs. However, to succeed in building nanoscale versions of the mechanical world, more understanding is required, rather than simple mimicry. In these chapters, I have studied the dynamics of molecular rotation in dendrimetric materials, MOFs crystal and organic solvents. With computational study, the rotational process is revealed at nanosecond time scale. New designs of molecular machine are proposed to improve their performance in different environments. Chapter 7 studies the rotation of phenyl rings at different parts in a dendrimeric material. Molecular dynamics study reveals the different dynamics of molecular rotations at the core, branches and peripheral ends. The energy surfaces of molecular rotation are scanned using umbrella sampling, and the energy barriers are computed. In Chapter 8, the rotational dynamics of molecular rotors in amphidynamic crystals are studied. The energy barriers of the rotation are computed by QM study to be ~0.2 kcal/mol, consistent with the ultrafast rotation in the rigid BODCA-MOF crystals. MD simulations reveal the ultrafast rotation at different temperatures and find it to be diffusion-like at high temperature. Chapter 9 compares and studies the gearing performance of different molecular spur gears. The gearing efficiency is affected by the distance between the two rotors in molecular gears. Solvent molecules are shown to interfere with the rotation of the molecular rotors and promote slippage rather than gearing. A new design of molecular spur gear is proposed and tested by MD simulations. With a macrocyclic structure, the solvent effect is eliminated and the molecular spur gear is able to gear in solvent phase.

Author : Arieh Warshel
Publisher : Wiley-Interscience
ISBN 13 :
Total Pages : 264 pages
Book Rating : 4.96/5 ( download)

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Download or read book Computer Modeling of Chemical Reactions in Enzymes and Solutions written by Arieh Warshel and published by Wiley-Interscience. This book was released on 1991-11-29 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practical reference explores computer modeling of enzyme reations--techniques that help chemists, biochemists and pharmaceutical researchers understand drug and enzyme action.