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.

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.

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.

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:

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.

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.

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.

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 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the last decade, there has been a significant shift from traditional mechanistic and empirical modelling into statistical and data-driven modelling for applications in reaction engineering. In particular, the integration of machine learning and first-principle models has demonstrated significant potential and success in the discovery of (bio)chemical kinetics, prediction and optimisation of complex reactions, and scale-up of industrial reactors. Summarising the latest research and illustrating the current frontiers in applications of hybrid modelling for chemical and biochemical reaction engineering, Machine Learning and Hybrid Modelling for Reaction Engineering fills a gap in the methodology development of hybrid models. With a systematic explanation of the fundamental theory of hybrid model construction, time-varying parameter estimation, model structure identification and uncertainty analysis, this book is a great resource for both chemical engineers looking to use the latest computational techniques in their research and computational chemists interested in new applications for their work.

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.

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.

Download or read book Quantum Tunnelling in Enzyme catalysed Reactions written by Rudolf K. Allemann and published by Royal Society of Chemistry. This book was released on 2009 with total page 412 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, there has been an explosion in knowledge and research associated with the field of enzyme catalysis and H-tunneling. Rich in its breath and depth, this introduction to modern theories and methods of study is suitable for experienced researchers those new to the subject. Edited by two leading experts, and bringing together the foremost practitioners in the field, this up-to-date account of a rapidly developing field sits at the interface between biology, chemistry and physics. It covers computational, kinetic and structural analysis of tunnelling and the synergy in combining these methods (with a major focus on H-tunneling reactions in enzyme systems). The book starts with a brief overview of proton and electron transfer history by Nobel Laureate, Rudolph A. Marcus. The reader is then guided through chapters covering almost every aspect of reactions in enzyme catalysis ranging from descriptions of the relevant quantum theory and quantum/classical theoretical methodology to the description of experimental results. The theoretical interpretation of these large systems includes both quantum mechanical and statistical mechanical computations, as well as simple more approximate models. Most of the chapters focus on enzymatic catalysis of hydride, proton and H" transfer, an example of the latter being proton coupled electron transfer. There is also a chapter on electron transfer in proteins. This is timely since the theoretical framework developed fifty years ago for treating electron transfers has now been adapted to H-transfers and electron transfers in proteins. Accessible in style, this book is suitable for a wide audience but will be particularly useful to advanced level undergraduates, postgraduates and early postdoctoral workers.

Download or read book Computational Approaches for Studying Enzyme Mechanism Part B written by and published by Academic Press. This book was released on 2016-08-03 with total page 538 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Approaches for Studying Enzyme Mechanism, Part B is the first of two volumes in the Methods in Enzymology series that focuses on computational approaches for studying enzyme mechanism. The serial achieves the critically acclaimed gold standard of laboratory practices and remains one of the most highly respected publications in the molecular biosciences. Each volume is eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with over 550 volumes, the series remains a prominent and essential publication for researchers in all fields of the life sciences and biotechnology, including biochemistry, chemical biology, microbiology, synthetic biology, cancer research, genetics, and other fields of study. Focuses on computational approaches for studying enzyme mechanism Continues the legacy of this premier serial with quality chapters authored by leaders in the field Covers research methods in intermediate filament associated proteins, and contains sections on such topics as lamin-associated proteins, intermediate filament-associated proteins and plakin, and other cytoskeletal cross-linkers

Download or read book Computational Approaches to Biochemical Reactivity written by Gábor Náray-Szabó and published by Springer. This book was released on 1997-04-30 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book summarises recent results in the rapidly developing discipline of the computational aspects of biochemical reactivity. It presents a comprehensive and critical treatise on the subject, with numerous references covering practically all relevant and recent work. The chapters, written by eminent experts in the field, deal with quantum mechanical models for reactions in solution, ab initio molecular orbital studies on enzymatic reactions, combined quantum-classical models for proteins, force field approaches for modelling enzymes, electrostatic effects in proteins, electrostatic basis of enzyme catalysis, the mechanism of proteases, modelling of proton transfer reactions in enzymes and protein-ligand interactions. Audience: This volume will be of interest to graduate students and researchers working in molecular biophysics, structural biology or structure-based molecular design.

Download or read book Computational Studies of Organic Organometallic and Enzyme Catalysis written by Elizabeth Lynn Noey and published by . This book was released on 2015 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computations are increasingly powerful tools for studying reaction mechanisms and protein catalysis. Various quantum mechanical (QM) and force field-based calculations are applied to problems in organic, organometallic, and protein chemistry. These studies span the chemistry-biology interface, progressing from theoretical studies of gold catalysis, to that of N-heterocyclic carbene (NHC) catalysis, and enzyme catalysis. The first study highlights a gold(I)-catalyzed enyne cyclization with a bifurcating potential energy surface. Several alkynylindoles undergo gold(I)-catalyzed cyclization reactions to form a single isomer in each case. This transformation involves a two-step no-intermediate mechanism with surface bifurcations leading to two or three products. The second gold study is on the mechanism of the rearrangement of acetylenic amine-N-oxides. Further work has been done on the mechanism of the Stetter reaction catalyzed by substituted NHCs. The leucine metabolic pathway was reengineered to produce biofuels, and computations showed that there is push-pull effect between the hydrophobic effect and steric clash, which dictates the LeuA substrate scope. The redesign of a transaminase to install the stereocenter in the blockbuster diabetes drug sitagliptin was attempted. The transaminase that was evolved for the industrial synthesis of sitagliptin, was studied computationally. This study elucidates the energetic details of the transamination mechanism to form sitagliptin, and makes progress toward understanding the role of mutations in the evolution. Finally, a computational, crystallographic, and kinetic study of ketoreductases (KREDs) shows how point mutations change the enantioselectively toward two small substrates, 3-oxa and 3-thiacyclopentanone. QM calculations of the ideal geometry for catalysis, and molecular dynamics (MD) simulations show how small changes in the size, shape, and hydrophobicity of the active site of the enzyme modulate the enantioselectively. Here, we develop an MD method, where simulations are run on the enzyme containing the theozyme for the reduction. This approach probes how well each enzyme stabilizes the transition structures and can predict the experimentally favored enantiomer. Although the subject matter varies, the underlying goal of understanding chemical reactions and catalysis from a physical organic perspective persists.

Download or read book Multi scale Quantum Models for Biocatalysis written by Darrin M. York and published by Springer Science & Business Media. This book was released on 2009-05-30 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: “Multi-scale Quantum Models for Biocatalysis” explores various molecular modelling techniques and their applications in providing an understanding of the detailed mechanisms at play during biocatalysis in enzyme and ribozyme systems. These areas are reviewed by an international team of experts in theoretical, computational chemistry, and biophysics. This book presents detailed reviews concerning the development of various techniques, including ab initio molecular dynamics, density functional theory, combined QM/MM methods, solvation models, force field methods, and free-energy estimation techniques, as well as successful applications of multi-scale methods in the biocatalysis systems including several protein enzymes and ribozymes. This book is an excellent source of information for research professionals involved in computational chemistry and physics, material science, nanotechnology, rational drug design and molecular biology and for students exposed to these research areas.

Download or read book The Dynamics of Enzymatic Reactions written by Lishan Yao and published by . This book was released on 2006 with total page 610 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book A Multiscale Computational Approach to Study RNase A Catalysis written by Thakshila D. Dissanayake Rallage and published by . This book was released on 2016 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: Enzyme catalysis is an extremely important and complex process that is fundamental to biology. Experiments provide a wealth of valuable information about the function of enzymes; however, this information requires the use of computational models to establish a meaningful interpretation that can be used to guide design. Multiscale computational models, which integrate a hierarchy of theoretical methods to address complex biomolecular problems that span large spatial and temporal ranges, afford powerful tools to provide a detailed molecular level interpretation of a wide range of experimental data from which a consensus view of catalytic mechanism may emerge. In this dissertation, I detail my efforts to develop and apply multiscale methods to study the mechanisms of RNA backbone cleavage catalyzed by Ribonuclease A, an important archetype enzyme system, and the factors that regulate its activity. In the first phase of this research, I use molecular dynamics simulations to characterize the structure and dynamics of the active enzyme in solution at different stages along the reaction path. In this work, I demonstrate that the crystallographic structure represents an inactive, catalytically non-relevant state, and make predictions that a conformational change involving the flipping of the side chain of a conserved histidine residue (His12) is required to adopt a catalytically competent conformation. In the second phase of this research, I apply ''constant pH molecular dynamics simulations'' (CpHMD) to characterize the conditional probability of finding key active site residues in a protonation state that supports general acid-base catalysis. This allowed the prediction of pKa shifts for His12, His119 and Lys41, and, for the first time, activity-pH profiles for an enzyme system that can be compared directly with those measured in kinetic experiments. In the third phase of this research, I use combined quantum mechanical/molecular mechanical methods to study the catalytic chemical steps of transphosphorylation. Results of this work predict a free energy landscape for the reaction, from which the minimum free energy pathway that connects reactants and products allows a detailed molecular-level picture of mechanism. In the fourth phase of this research, I extend the CpHMD method to nucleic acid systems, to benchmark the method for the study of ribozymes that catalyze the same reaction as RNase A.