Interfacial Modulation of Protein Function Explored Through Atomistic Molecular Dynamics Simulation PDF Download

Author: Joshua V. Vermaas
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Yao Xu
Publisher:
ISBN:
Category : Electronic books
Languages : en
Pages : 332

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Clusters of water molecules embedded in proteins or at the interface between globules mediate protein dynamics, allostery and charge transfer. Confined clusters of water molecules exhibit dynamics distinct from dynamics of water in the bulk or in the hydration layer around biomolecules. Here, we describe and compare the dynamics of water in the hydration layer around antifreeze proteins, the dynamics of a cluster of water molecules at the interface between the globules of a homodimeric hemoglobin, and the dynamics of water molecules within green fluorescent protein (GFP) and the hydration water in the vicinity of photoactive yellow protein (PYP), all studied by molecular dynamics simulations. The water dynamics in these systems span a wide range of time scales and are closely related to function, ranging from relatively fast hydration water dynamics to tightly bound water clusters that mediate protein conformational change during ligand binding. Subsequent quantum mechanical studies on energy relaxation in proteins GFP and PYP provide insights into the microenvironment of the chromophore and identify energy flow channels that may mediate the kinetics of photochemical reactions such as charge transfer and conformational isomerization.

Author: Dineli Thakshila Sarasavi Ranathunga
Publisher:
ISBN:
Category : Absorption
Languages : en
Pages : 0

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In this dissertation molecular dynamics computer simulations (MD) were used to explore molecular scale behavior in order to interpret experimental results and guide challenging experimental work. In Chapters 2, 3 and 4 MD simulations were utilized to study a new immunointeractive surface approach to induce titanium implant osseointegration, using the constructive inflammatory effects of high mobility group box 1 (HMGB1) protein. First, in Chapter 2 the protein, ion and water interactions with the rutile (110) TiO2 surface induced by surface hydroxylation were investigated. In an aqueous environment, we show the direct binding of HMGB1 to the TiO2 surface regardless of its hydroxylation state, which causes structural changes to the protein, thereby affecting its biological function. Hence, to find a compromise between stable adsorption and preservation of protein activity in Chapter 3 we study the advantages of dicationic imidazolium-based ionic liquids (IonLs) containing amino acid anions to serve as a vehicle for delivering proteins on the surface of TiO2 implants. A strongly bound well structured IonL coating formed on the TiO2 surface effectively blocking HMGB1 from direct adsorption on the implant. Additionally, the protein is immobilized due to IonL cations and anions which bind to oppositely charged amino acids on the protein surface. In order to account for the different biological roles of HMGB1, the different HMGB1 isoforms were studied in Chapter 4. Once the IonL/HMGB1 coating on the TiO2 surface comes into contact with water, the protein release mechanism and the integrity of its receptor binding sites were investigated. Imidazolium based IonLs are becoming increasingly popular not only in bioengineering but also in many other fields due to their promising properties. Because of the large number of cation and anion combinations available, it is not feasible to experimentally measure IonL properties over a wide range of composition and operating conditions. Therefore, fast and reliable methods such as molecular modeling tools are needed to acquire these properties. However, to validate and tune the molecular modeling approach some experimental data is required. Therefore, in Chapter 5 by combining experiments with molecular modeling we explore the properties of a series of IonLs. In Chapter 6, we used MD simulations to study vapor condensation which is an area with a wide range of industrial applications. We provide molecular insight into the condensation mechanism as a function of surface wettability using surfaces chemisorbed with alkanethiol self-assembled monolayers. By changing the alkanethiol head group chemistry, the surface wettability was tuned and the role of surface wettability on the rate of water condensation was studied. We show that decreasing surface hydrophobicity significantly increases the electrostatic forces between water molecules and the surface, thus increasing the water condensation rate. We also provide connections with other microscopic and macroscopic interfacial characterizations. In Chapter 7, we used MD simulations to link experimentally observed anion sensing, specifically towards nitrate, nitrite, iodide, and thiocyanate by polyvinylpyrrolidone (PVP) polymer, to anion interactions on the polymer surface and concomitant changes in the polymer aggregation state. Supporting the experimental observations, our results suggest that anions associating most strongly to the surface of PVP quench its fluorescence to the greatest extent.

Author: Christophe Chipot
Publisher: Springer Science & Business Media
ISBN: 3540384472
Category : Language Arts & Disciplines
Languages : en
Pages : 528

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Free energy constitutes the most important thermodynamic quantity to understand how chemical species recognize each other, associate or react. Examples of problems in which knowledge of the underlying free energy behaviour is required, include conformational equilibria and molecular association, partitioning between immiscible liquids, receptor-drug interaction, protein-protein and protein-DNA association, and protein stability. This volume sets out to present a coherent and comprehensive account of the concepts that underlie different approaches devised for the determination of free energies. The reader will gain the necessary insight into the theoretical and computational foundations of the subject and will be presented with relevant applications from molecular-level modelling and simulations of chemical and biological systems. Both formally accurate and approximate methods are covered using both classical and quantum mechanical descriptions. A central theme of the book is that the wide variety of free energy calculation techniques available today can be understood as different implementations of a few basic principles. The book is aimed at a broad readership of graduate students and researchers having a background in chemistry, physics, engineering and physical biology.

Author: Daniel E. Atkinson
Publisher:
ISBN:
Category : Science
Languages : en
Pages : 516

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Author: Defang Ouyang
Publisher: John Wiley & Sons
ISBN: 1118573994
Category : Science
Languages : en
Pages : 350

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Molecular modeling techniques have been widely used in drug discovery fields for rational drug design and compound screening. Now these techniques are used to model or mimic the behavior of molecules, and help us study formulation at the molecular level. Computational pharmaceutics enables us to understand the mechanism of drug delivery, and to develop new drug delivery systems. The book discusses the modeling of different drug delivery systems, including cyclodextrins, solid dispersions, polymorphism prediction, dendrimer-based delivery systems, surfactant-based micelle, polymeric drug delivery systems, liposome, protein/peptide formulations, non-viral gene delivery systems, drug-protein binding, silica nanoparticles, carbon nanotube-based drug delivery systems, diamond nanoparticles and layered double hydroxides (LDHs) drug delivery systems. Although there are a number of existing books about rational drug design with molecular modeling techniques, these techniques still look mysterious and daunting for pharmaceutical scientists. This book fills the gap between pharmaceutics and molecular modeling, and presents a systematic and overall introduction to computational pharmaceutics. It covers all introductory, advanced and specialist levels. It provides a totally different perspective to pharmaceutical scientists, and will greatly facilitate the development of pharmaceutics. It also helps computational chemists to look for the important questions in the drug delivery field. This book is included in the Advances in Pharmaceutical Technology book series.

Author: Bruce J Berne
Publisher: World Scientific
ISBN: 9814496057
Category : Science
Languages : en
Pages : 881

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The school held at Villa Marigola, Lerici, Italy, in July 1997 was very much an educational experiment aimed not just at teaching a new generation of students the latest developments in computer simulation methods and theory, but also at bringing together researchers from the condensed matter computer simulation community, the biophysical chemistry community and the quantum dynamics community to confront the shared problem: the development of methods to treat the dynamics of quantum condensed phase systems.This volume collects the lectures delivered there. Due to the focus of the school, the contributions divide along natural lines into two broad groups: (1) the most sophisticated forms of the art of computer simulation, including biased phase space sampling schemes, methods which address the multiplicity of time scales in condensed phase problems, and static equilibrium methods for treating quantum systems; (2) the contributions on quantum dynamics, including methods for mixing quantum and classical dynamics in condensed phase simulations and methods capable of treating all degrees of freedom quantum-mechanically.

Author: Qiang Cui
Publisher: CRC Press
ISBN: 142003507X
Category : Mathematics
Languages : en
Pages : 448

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Rapid developments in experimental techniques continue to push back the limits in the resolution, size, and complexity of the chemical and biological systems that can be investigated. This challenges the theoretical community to develop innovative methods for better interpreting experimental results. Normal Mode Analysis (NMA) is one such technique

Author: Aihua Zhang
Publisher: John Wiley & Sons
ISBN: 3527835741
Category : Science
Languages : en
Pages : 292

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Highlights the importance and benefit of mass spectrometry-based metabolomics for identifying biomarkers that accurately screen for potential biomarkers of diseases Mass spectrometry-based metabolomics offer new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has been applied to discovering and identifying the perturbed pathways. Currently, mass spectrometry-based metabolomics has become an important tool in clinical research and the diagnosis of human disease. Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines comprehensively presents the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics such as metabolites analysis, biomarker discovery, technical challenges, discovery of natural product, mechanism interpretation of action, discovery of active ingredients, clinical application and precision medicine, and enhancing their biomedical value in a real world of biomedicine, shedding light on the potential for spectrometry-based metabolomics. It highlights the value of mass spectrometry-based metabolomics and metabolism to address the complexity of herbal medicines in systems pharmacology, especially, to link phytochemical analysis with the assessment of pharmacological effect and therapeutic potential. Each chapter has been laid out with introduction, method, up-to-date literature, identification of biomarker, and applications Covers the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics in the discovery of biomarker, active ingredients, natural product, etc. Constitutes a unique and indispensable practical guide for any phytochemistry or related laboratory, and provides hands-on description of new techniques Provides a guide for new practitioners of pharmacologists, pharmacological scholars, drug developers, botanist, researchers of traditional medicines. Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines provides a landmark of mass spectrometry-based metabolomics research and a beneficial guideline to graduate students and researchers in academia, industry, and technology transfer organizations in all biomedical science fields.

Author: Jia Fu
Publisher: BoD – Books on Demand
ISBN: 1838802010
Category : Computers
Languages : en
Pages : 180

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Multiscale simulations of atomistic/continuum coupling in computational materials science, where the scale expands from macro-/micro- to nanoscale, has become a hot research topic. These small units, usually nanostructures, are commonly anisotropic. The development of molecular modeling tools to describe and predict the mechanical properties of structures reveals an undeniable practical importance. Typical anisotropic structures (e.g. cubic, hexagonal, monoclinic) using DFT, MD, and atomic finite element methods are especially interesting, according to the modeling requirement of upscaling structures. It therefore connects nanoscale modeling and continuous patterns of deformation behavior by identifying relevant parameters from smaller to larger scales. These methodologies have the prospect of significant applications. I would like to recommend this book to both beginners and experienced researchers.