Download or read book Multiscale Modeling of Metalloenzymes Design and Evolution written by Michael Nechay and published by . This book was released on 2017 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: With just a simple alphabet of natural amino acids and common metals, enzymes perform a spectacular number of reactions necessary for life on earth with enviable ease - with neither the extreme conditions nor chemical waste seen from many industrial reactors in human-developed catalysis. Principally, protein structure and related function is not well understood beyond being decisive for its unique selectivity and efficiency. A reliable treatment of larger protein movements/sampling coupled with precise quantum mechanical treatment of metals and bonds breaking/forming (multiscale) is still an open problem in Computational Chemistry. Metalloenzymes can be particularly challenging to model so we present some of the latest in multiscale modeling techniques. We have developed methods sensitive enough to study "selection" of similar metals in enzymes such as HDAC8, where previous literature failed to conclude which metal is active during in vivo catalysis, while fast enough to study larger protein movements including fold stability. Eminently, multiscale modeling opens the discussion of engineering enzymes to cater to modern day needs in catalysis. Society has not only developed needs in catalysis outside the scope of natural evolution (e.g., drug synthesis, energy conversion) but also has access to more of the periodic table than nature has had a chance to explore. Thus, combining the efficacy of natural enzymes with modern catalytic processes has enormous potential. We have studied iridium, a rare metal with thermodynamic advantages over other metals in promoting catalysis of hydroamination and transfer hydrogenation. In the context of an enzyme we predict catalytic rates near and even exceeding existing organometallic catalysts with further design for specificity available. We are in collaboration with an experimental group in designing a protein fold which both directly accommodates and uses iridium in catalysis. We hope these foundations will support metalloenzyme design efforts towards novel chemical transformations performed as efficiently and environmentally soundly as nature has shown us is possible.
Download or read book Design and Evolution of Metalloenzymes Through Multi scale Approaches written by Crystal Edie Valdez and published by . This book was released on 2015 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: Natural metalloenzymes are often the most proficient catalysts in terms of their activity, selectivity, and ability to operate at mild conditions. However, metalloenzymes are occasionally surprising in their choice of catalytic metals, and in their responses to metal substitution. Indeed, from the isolated standpoint of producing the best catalyst, a chemist designing from first principles would likely choose a different metal. Due to competing evolutionary pressures, many natural enzymes may not have evolved to be ideal catalysts and can be improved for the isolated purpose of catalysis in vitro when the competing factors are removed. To improve and, in due course, design metalloenzymes, extensive sampling and proper treatment of the electronic structure of the bound metal(s), is required, while seamlessly merging the required techniques to assess energies and entropies, or their changes, for the entire system. Approaching these challenges with a multi-scale approach, the Alexandrova group has developed an accurate and efficient quantum mechanical/molecular mechanics (QM/MM) hybrid dynamics method to model metalloproteins called quantum mechanics/discrete molecular mechanics (QM/DMD). QM/DMD operates through an iterative scheme between QM and MM machineries. DMD is a flavor of molecular dynamics (MD) that approximates the continuous interaction potentials in classical MD with square-well potentials, course-graining the potentials and overall reducing the number of calculations needed. Due to these discretized potentials, DMD is driven by collision events rather than physical forces as in traditional MM and MD. Therefore, the user saves a tremendous amount of time with DMD by solving ballistic equations of motions rather than Newtonian equations of motions. This fast and efficient hybrid dynamics tools has allowed us to investigate various metal-dependent phenomena in natural metalloenzymes such as: 1) exploring Nature's curious choices for specific metals using two amide hydrolases that contain different metals as a case study, 2) examining protein conformational responses to substrate binding and metal replacement as showcased by the role of a flexible loop [beta]-lactamase in binding antibiotic substrates and 3) investigating how the species of the metal dictates the reaction mechanism in a pair acireductone dioxygenases (ARD/ARD'). Extending outside the realm of naturally occurring enzymes, our tools have the ability to span across formidable challenges such as metalloenzyme design, where stabilization of a transition state of the catalyzed reaction in the specific binding pocket around the metal needs to be achieved. QM/DMD was used in the redesign of a well-studied Zn2+ peptidase, carboxypeptidase A (CPA), an enzyme involved in the breakdown of proteins, with a slight preference for bulky hydrophobic groups. More specifically, the enzyme and substrate system were modified to create specific-specific binding and subsequent experiments proved the mutant to be catalytically active. Additionally, another tool called Eris-QM/DMD was formulated to better gauge the effect of mutation on protein structure during the design process. Eris is a stand-alone package that evaluates protein stability upon mutagenesis. Coupling the software to QM/DMD gives us the distinct advantage of accounting for the effect of the metal during protein alternations. With this diverse set of tools, our future ambitious goals are to install catalytically potent non-physiological metals into proteins. While nature is limited to operating with bio-available elements, some metals such as Ir, Pd, Sc, and Rh, which have been shown to be excellent catalysts, even surpassing physiological metals. If the catalytic activity of these non-physiological metals can be combined with the superb selectivity and mild operational conditions characteristic of proteins, new proficient enzymes may emerge. Another advantage to enzymatic catalysis, done either in vitro, or in vivo, is that it can be cheaper, "greener", and more efficient than synthetic catalysis. An early endeavor in this frontier of metalloenzyme design involves installing Pd2+ into an existing protein scaffold, specifically for intramolecular hydroarylation of C-C triple bonds to form coumarins.
Download or read book Artificial Metalloenzymes and MetalloDNAzymes in Catalysis written by Montserrat Diéguez and published by John Wiley & Sons. This book was released on 2018-06-05 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: An important reference for researchers in the field of metal-enzyme hybrid catalysis Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a comprehensive review of the most current strategies, developed over recent decades, for the design, synthesis, and optimization of these hybrid catalysts as well as material about their application. The contributors—noted experts in the field—present information on the preparation, characterization, and optimization of artificial metalloenzymes in a timely and authoritative manner. The authors present a thorough examination of this interesting new platform for catalysis that combines the excellent selective recognition/binding properties of enzymes with transition metal catalysts. The text includes information on the various applications of metal-enzyme hybrid catalysts for novel reactions, offers insights into the latest advances in the field, and contains an informative perspective on the future: Explores the development of artificial metalloenzymes, the modern and strongly evolving research field on the verge of industrial application Contains a comprehensive reference to the research area of metal-enzyme hybrid catalysis that has experienced tremendous growth in recent years Includes contributions from leading researchers in the field Shows how this new catalysis combines the selective recognition/binding properties of enzymes with transition metal catalysts Written for catalytic chemists, bioinorganic chemists, biochemists, and organic chemists, Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a unique reference to the fundamentals, concepts, applications, and the most recent developments for more efficient and sustainable synthesis.
Download or read book Designed Evolution of Artificial Metalloenzymes Protein Catalysts Made to Order written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Artificial metalloenzymes based on biotin- treptavidin technology, a fusion of chemistry and biology, illustrate how asymmetric catalysts can be improved and evolved using chemogenetic approaches.
Download or read book Multiscale Modeling of Metalloproteins and Protonation Equilibria in Biomolecular Systems written by Patrick G. Blachly and published by . This book was released on 2014 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt: A combination of classical and quantum mechanical approaches are described in Chapter 1 and utilized in this dissertation to study catalysis and allostery in the metalloprotein IspH, as well as to probe protonation equilibria in a variety of macromolecules. Chapters 2 and 3 are dedicated to characterizing the oxidized [4Fe-4S] IspH protein, which is biologically important as an antimicrobial drug target. In Chapter 2, the protonation states of active site residues in substrate-bound IspH are characterized using broken-symmetry density functional theory to provide a foundation for exploring IspH catalysis. Subsequently, a more coarse-grained approach is used in Chapter 3 to assess the internal motions of IspH, both with and without its substrate bound, using classical molecular dynamics. Both these studies reveal rational approaches for the design of novel IspH inhibitors. Chapters 4 and 5 deviate from the metalloprotein theme established in Chapters 2 and 3 to consider classical approaches for treating proton binding and unbinding in the context of molecular dynamics simulations. The ability of the constant pH molecular dynamics method to predict protein pKa values is assessed in Chapter 4 using an experimental test set comprising Staphylococcal nuclease variants. Building on this work, Chapter 5 provides proof of concept for the constant pH molecular dynamics method to obtain pH-dependent binding free energies in conjunction with Wyman's binding polynomial formalism.
Download or read book Artificial Metalloenzymes and MetalloDNAzymes in Catalysis written by Montserrat Diéguez and published by John Wiley & Sons. This book was released on 2018-02-21 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: An important reference for researchers in the field of metal-enzyme hybrid catalysis Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a comprehensive review of the most current strategies, developed over recent decades, for the design, synthesis, and optimization of these hybrid catalysts as well as material about their application. The contributors—noted experts in the field—present information on the preparation, characterization, and optimization of artificial metalloenzymes in a timely and authoritative manner. The authors present a thorough examination of this interesting new platform for catalysis that combines the excellent selective recognition/binding properties of enzymes with transition metal catalysts. The text includes information on the various applications of metal-enzyme hybrid catalysts for novel reactions, offers insights into the latest advances in the field, and contains an informative perspective on the future: Explores the development of artificial metalloenzymes, the modern and strongly evolving research field on the verge of industrial application Contains a comprehensive reference to the research area of metal-enzyme hybrid catalysis that has experienced tremendous growth in recent years Includes contributions from leading researchers in the field Shows how this new catalysis combines the selective recognition/binding properties of enzymes with transition metal catalysts Written for catalytic chemists, bioinorganic chemists, biochemists, and organic chemists, Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a unique reference to the fundamentals, concepts, applications, and the most recent developments for more efficient and sustainable synthesis.
Download or read book Comprehensive Asymmetric Catalysis written by Eric N. Jacobsen and published by Springer Science & Business Media. This book was released on 2003-09-22 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first supplement to the three volume reference work "Comprehensive Asymmetric Catalysis" critically reviews new developments to the hottest topics in the field written by recognised experts. Eleven chapters which are already in the major reference work have been supplemented and additionally five new chapters have been included. Thus the state-of-the art in this area is now re-established. Together with the basic three volume book set this supplement is not only the principal reference source for synthetic organic chemists, but also for all scientific researchers who use chiral compounds in their work (for example, in biochemical investigations and molecular medicine) as well as for pharmaceutical chemists and other industrial researchers who prepare chiral compounds.
Download or read book Nanozymes Next Wave of Artificial Enzymes written by Xiaoyu Wang and published by Springer. This book was released on 2016-07-27 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes the fundamental concepts, the latest developments and the outlook of the field of nanozymes (i.e., the catalytic nanomaterials with enzymatic characteristics). As one of today’s most exciting fields, nanozyme research lies at the interface of chemistry, biology, materials science and nanotechnology. Each of the book’s six chapters explores advances in nanozymes. Following an introduction to the rise of nanozymes research in the course of research on natural enzymes and artificial enzymes in Chapter 1, Chapters 2 through 5 discuss different nanomaterials used to mimic various natural enzymes, from carbon-based and metal-based nanomaterials to metal oxide-based nanomaterials and other nanomaterials. In each of these chapters, the nanomaterials’ enzyme mimetic activities, catalytic mechanisms and key applications are covered. In closing, Chapter 6 addresses the current challenges and outlines further directions for nanozymes. Presenting extensive information on nanozymes and supplemented with a wealth of color illustrations and tables, the book offers an ideal guide for readers from disparate areas, including analytical chemistry, materials science, nanoscience and nanotechnology, biomedical and clinical engineering, environmental science and engineering, green chemistry, and novel catalysis.
Download or read book Chemical Abstracts written by and published by . This book was released on 2002 with total page 2800 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Computational Catalysis written by Aravind Asthagiri and published by Royal Society of Chemistry. This book was released on 2014 with total page 277 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents a comprehensive review of the methods and approaches being adopted to push forward the boundaries of computational catalysis.
Download or read book Bioinorganic Catalysis written by Jan Reedijk and published by CRC Press. This book was released on 1999-02-02 with total page 628 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Provides the latest research results and suggests new topics for interdisciplinary study of metal ions, catalysis, and biochemical systems. Second Edition highlights potential applications; includes new chapters on zinc and FeS clusters; presents new X-ray analysis of metalloenzymes; and more."
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 Supramolecular Catalysis written by Piet W.N.M. van Leeuwen and published by John Wiley & Sons. This book was released on 2021-12-31 with total page 708 pages. Available in PDF, EPUB and Kindle. Book excerpt: Supramolecular Catalysis Provides a timely and detailed overview of the expanding field of supramolecular catalysis The subdiscpline of supramolecular catalysis has expanded in recent years, benefiting from the development of homogeneous catalysis and supramolecular chemistry. Supramolecular catalysis allows chemists to design custom-tailored metal and organic catalysts by devising non-covalent interactions between the various components of the reaction. Edited by two world-renowned researchers, Supramolecular Catalysis: New Directions and Developments summarizes the most significant developments in the dynamic, interdisciplinary field. Contributions from an international panel of more than forty experts address a broad range of topics covering both organic and metal catalysts, including emergent catalysis by self-replicating molecules, switchable catalysis using allosteric effects, supramolecular helical catalysts, and transition metal catalysis in confined spaces. This authoritative and up-to-date volume: Covers ligand-ligand interactions, assembled multi-component catalysts, ligand-substrate interactions, and supramolecular organocatalysis and non-classical interactions Presents recent work on supramolecular catalysis in water, supramolecular allosteric catalysis, and catalysis promoted by discrete cages, capsules, and other confined environments Highlights current research trends and discusses the future of supramolecular catalysis Includes full references and numerous figures, tables, and color illustrations Supramolecular Catalysis: New Directions and Developments is essential reading for catalytic chemists, complex chemists, biochemists, polymer chemists, spectroscopists, and chemists working with organometallics.
Download or read book Graduate Programs in the Physical Sciences Mathematics Agricultural Sciences the Environment and Natural Resources 2009 written by Peterson's and published by Peterson Nelnet Company. This book was released on 2007-11 with total page 776 pages. Available in PDF, EPUB and Kindle. Book excerpt: The six volumes of Peterson's Annual Guides to Graduate Study, the only annually updated reference work of its kind, provide wide-ranging information on the graduate and professional programs offered by accredited colleges and universities in the United States and U.S. territories and those in Canada, Mexico, Europe, and Africa that are accredited by U.S. accrediting bodies. Books 2 through 6 are divided into sections that contain one or more directories devoted to individual programs in a particular field. Book 4 contains more than 3,800 programs of study in 56 disciplines of the physical sciences, mathematics, agricultural sciences, the environment, and natural resources.
Download or read book Directed Evolution of Selective Enzymes written by Manfred T. Reetz and published by John Wiley & Sons. This book was released on 2016-12-19 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Authored by one of the world's leading organic chemists, this authoritative reference provides an overview of basic strategies in directed evolution and introduces common gene mutagenesis, screening and selection methods. Throughout the text, emphasis is placed on methodology development to maximize efficiency, reliability and speed of the experiments and to provide guidelines for efficient protein engineering. Professor Reetz highlights the application of directed evolution experiments to address limitations in the field of enzyme selectivity, substrate scope, activity and robustness. He critically reviews recent developments and case studies, takes a look at future applications in the field of organic synthesis, and concludes with lessons learned from previous experiments.
Download or read book Mathematical Models in Biology written by Leah Edelstein-Keshet and published by SIAM. This book was released on 1988-01-01 with total page 629 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mathematical Models in Biology is an introductory book for readers interested in biological applications of mathematics and modeling in biology. A favorite in the mathematical biology community, it shows how relatively simple mathematics can be applied to a variety of models to draw interesting conclusions. Connections are made between diverse biological examples linked by common mathematical themes. A variety of discrete and continuous ordinary and partial differential equation models are explored. Although great advances have taken place in many of the topics covered, the simple lessons contained in this book are still important and informative. Audience: the book does not assume too much background knowledge--essentially some calculus and high-school algebra. It was originally written with third- and fourth-year undergraduate mathematical-biology majors in mind; however, it was picked up by beginning graduate students as well as researchers in math (and some in biology) who wanted to learn about this field.
Download or read book Bioinspiration and Biomimicry in Chemistry written by Gerhard Swiegers and published by John Wiley & Sons. This book was released on 2012-09-17 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: Can we emulate nature's technology in chemistry? Through billions of years of evolution, Nature has generated some remarkable systems and substances that have made life on earth what it is today. Increasingly, scientists are seeking to mimic Nature's systems and processes in the lab in order to harness the power of Nature for the benefit of society. Bioinspiration and Biomimicry in Chemistry explores the chemistry of Nature and how we can replicate what Nature does in abiological settings. Specifically, the book focuses on wholly artificial, man-made systems that employ or are inspired by principles of Nature, but which do not use materials of biological origin. Beginning with a general overview of the concept of bioinspiration and biomimicry in chemistry, the book tackles such topics as: Bioinspired molecular machines Bioinspired catalysis Biomimetic amphiphiles and vesicles Biomimetic principles in macromolecular science Biomimetic cavities and bioinspired receptors Biomimicry in organic synthesis Written by a team of leading international experts, the contributed chapters collectively lay the groundwork for a new generation of environmentally friendly and sustainable materials, pharmaceuticals, and technologies. Readers will discover the latest advances in our ability to replicate natural systems and materials as well as the many impediments that remain, proving how much we still need to learn about how Nature works. Bioinspiration and Biomimicry in Chemistry is recommended for students and researchers in all realms of chemistry. Addressing how scientists are working to reverse engineer Nature in all areas of chemical research, the book is designed to stimulate new discussion and research in this exciting and promising field.
