Download or read book Molecular Dynamic Simulations of the Interaction of Natural Compounds with Lipid Bilayer Membranes written by Gabin Fabre and published by . This book was released on 2012 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt: Based on the structures of natural molecules, many new derivatives are continuously synthetized to enhance therapeutic. To understand the mechanism of action of these compounds, one of the key steps is the capacity to incorporate/cross lipid bilayer membranes. Molecular dynamics (MD) has recently appeared as a powerful tool to rationalize these interactions at the molecular level. Here we report on two different types of derivatives. The first class concerns antioxidants. One of the most important oxidative processes in the organism is lipid peroxidation in cell membrane. To efficiently stop lipid peroxidation, potential antioxidants have to (i) scavenge free radicals and (ii) incorporate inside the membrane. Lipocarbazole exhibits an efficient antioxidant activity against lipid peroxidation in vitro, which can be correlated to its actual position and orientation inside the membrane. The second class concerns antibacterials. Plantazolicin A exhibits antibacterial activity against Gram+ strains. In order to understand this activity (i) the 3D re-arrangement and (ii) its interaction with bacterial membrane must be fully understood. Using a model of lipid bilayer membrane, the capacity of this compound to form pores is evaluated here.
Download or read book Novel Approaches to the Structure and Dynamics of Liquids Experiments Theories and Simulations written by Vladimir A. Durov and published by Springer Science & Business Media. This book was released on 2004 with total page 568 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Biological Membranes written by Kenneth M. Merz and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 596 pages. Available in PDF, EPUB and Kindle. Book excerpt: The interface between a living cell and the surrounding world plays a critical role in numerous complex biological processes. Sperm/egg fusion, virus/cell fusion, exocytosis, endocytosis, and ion permeation are a few examples of processes involving membranes. In recent years, powerful tools such as X-ray crystal lography, electron microscopy, nuclear magnetic resonance, and infra-red and Raman spectroscopy have been developed to characterize the structure and dy namics of biomembranes. Despite this progress, many of the factors responsible for the function of biomembranes are still not well understood. The membrane is a very complicated supramolecular liquid-crystalline structure that is largely composed of lipids, forming a bilayer, to which proteins and other biomolecules are anchored. Often, the lipid bilayer environment is pictured as a hydropho bic structureless slab providing a thermodynamic driving force to partition the amino acids of a membrane protein according to their solubility. However, much of the molecular complexity of the phospholipid bilayer environment is ignored in such a simplified view. It is likely that the atomic details of the polar head group region and the transition from the bulk water to the hydrophobic core of the membrane are important. An understanding of the factors responsible for the function of biomembranes thus requires a better characterization at the molec ular level of how proteins interact with lipid molecules, of how lipids affect protein structure and of how lipid molecules might regulate protein function.
Download or read book Current Frontiers in Cryobiology written by Igor Katkov and published by BoD – Books on Demand. This book was released on 2012-03-09 with total page 596 pages. Available in PDF, EPUB and Kindle. Book excerpt: Almost a decade has passed since the last textbook on the science of cryobiology, Life in the Frozen State, was published. Recently, there have been some serious tectonic shifts in cryobiology which were perhaps not seen on the surface but will have a profound effect on both the future of cryobiology and the development of new cryopreservation methods. We feel that it is time to revise the previous paradigms and dogmas, discuss the conceptually new cryobiological ideas, and introduce the recently emerged practical protocols for cryopreservation. The present books, "Current Frontiers in Cryobiology" and "Current Frontiers in Cryopreservation" will serve the purpose. This is a global effort by scientists from 27 countries from all continents and we hope it will be interesting to a wide audience.
Download or read book Computational Pharmaceutics written by Defang Ouyang and published by John Wiley & Sons. This book was released on 2015-07-20 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Molecular Simulations and Biomembranes written by Mark S P Sansom and published by Royal Society of Chemistry. This book was released on 2010-08-01 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: The need for information in the understanding of membrane systems has been caused by three things - an increase in computer power; methodological developments and the recent expansion in the number of researchers working on it worldwide. However, there has been no up-to-date book that covers the application of simulation methods to membrane systems directly and this book fills an important void in the market. It provides a much needed update on the current methods and applications as well as highlighting recent advances in the way computer simulation can be applied to the field of membranes and membrane proteins. The objectives are to show how simulation methods can provide an important contribution to the understanding of these systems. The scope of the book is such that it covers simulation of membranes and membrane proteins, but also covers the more recent methodological developments such as coarse-grained molecular dynamics and multiscale approaches in systems biology. Applications embrace a range of biological processes including ion channel and transport proteins. The book is wide ranging with broad coverage and a strong coupling to experimental results wherever possible, including colour illustrations to highlight particular aspects of molecular structure. With an internationally respected list of authors, its publication is timely and it will prove indispensable to a large scientific readership.
Download or read book Probing Lipid Membrane Interactions with Drug Molecules and Cationic Proteins Using Combined Experimental and Computational Analysis written by Lorena Alvarez and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The lipid bilayer's integrity is essential for cell function as it acts as the primary barrier against external molecules like drugs and peptides, which can alter the bilayer's physical properties. This dissertation investigates how amphetamine (AMPH) and methamphetamine (METH), and the charged HIV1-TAT peptide impact the stability of lipid bilayers, using a home-built lipid bilayer apparatus that enables real-time monitoring through electrical and fluorescence measurements. Our findings indicate that AMPH and METH increase the lipid bilayer's ion permeability, with METH having a greater destabilizing effect. High concentrations of these stimulants, akin to levels in blood plasma of individuals with stimulant-related brain injuries, lead to pore formation in the bilayer. The extent of destabilization correlated with the drug concentration. We also studied the translocation dynamics of the charged HIV1-TAT peptide across the lipid bilayer. The analysis of current fluctuations showed that successful translocation of the TAT peptide is concentration-dependent, highlighting the significance of charge in inducing membrane deformation or pore formation. Additionally, molecular dynamic simulations were used to explore AMPH interactions with the lipid bilayer in greater detail. The results revealed AMPH's preferred orientation during interaction and its hydrophobic nature, as evidenced by the larger energy barrier encountered in the hydrophilic head group regions of the lipid bilayer. To complement these findings, we utilized surface-enhanced Raman spectroscopy (SERS) to estimate the concentrations of AMPH within lipid bilayers. The data showed a positive correlation between characteristic peak heights and AMPH concentrations. Moreover, whole-cell patch clamp measurements on neuronal cells were employed to examine AMPH's effects in a more intricate lipid environment. This research contributes to the understanding of how stimulants and charged peptides interact with lipid bilayers, which is vital for insights into their biological impacts and in developing therapeutic interventions.
Download or read book Peptide Lipid Interactions written by Sidney A. Simon and published by Academic Press. This book was released on 2002-11-13 with total page 606 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume contains a comprehensive overview of peptide-lipid interactions by leading researchers. The first part covers theoretical concepts, experimental considerations, and thermodynamics. The second part presents new results obtained through site-directed EPR, electron microscopy, NMR, isothermal calorimetry, and fluorescence quenching. The final part covers problems of biological interest, including signal transduction, membrane transport, fusion, and adhesion. Key Features * world-renowned experts * state-of-the-art experimental methods * monolayers, bilayers, biological membranes * theoretical aspects and computer simulations * rafts * synaptic transmission * membrane fusion * signal transduction
Download or read book Coupling and Clustering in Molecular Dynamics Simulation Studies of Lipid Membrane Biophysics written by Michael David Weiner and published by . This book was released on 2018 with total page 452 pages. Available in PDF, EPUB and Kindle. Book excerpt: The plasma membrane defines a eukaryotic cell, separating the cell's interior from its surroundings. Structurally, the plasma membrane is a lipid bilayer, composed of numerous different lipids and proteins. A biophysical approach to understanding this system examines the behavior of the liquid crystal phases of the membrane's lipids. In particular, membrane rafts, regions with distinct physical properties, may be studied in model membranes using coexisting liquid phases containing as few as three lipid components. The findings described in this dissertation employ Molecular Dynamics simulations, computational models of the physics of interacting atoms and molecules, to explore the biophysical chemistry of lipid bilayers. Coarse-grained Molecular Dynamics simulations use simplified molecular models, which makes reproducing spontaneous demixing into coexisting liquid phases computationally feasible. The first study presented uses coarse-grained simulations to examine coupling between the two leaflets of a model membrane. While most publications report alignment of like domains, this study shows that lengthening the acyl chains of the high-melting-temperature phospholipid component or increasing the cholesterol concentration yields an alignment of unlike domains, accompanied by the appearance of a significant presence of cholesterol at the bilayer midplane, between the leaflets. The second study takes a different approach to leaflet coupling, engaging in atomistic simulations of compositionally asymmetric bilayers. Different lipids are present in each leaflet of the plasma membrane, so an asymmetric composition offers a more physiological model. The work reveals that even a single-phase leaflet is coupled to a phase-separated leaflet, as it adopts slightly different physical properties in the regions interacting with different domains. This finding suggests that transmembrane communication through coupling can occur in cells. Finally, the third study considers the role of ions in clusters of phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid that makes up a small fraction of the plasma membrane but plays an outsize role in cell signaling and the retrovirus lifecycle. It confirms experimental evidence that clusters form in the presence of divalent cations but not monovalent ones and examines the interaction of ions and lipids and the impact on the lipids' physical properties.
Download or read book Lipid Bilayers written by J. Katsaras and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides the reader with an up to date insight of the current state of the art in the field of lipid bilayer research and the important insights derived for the understanding of the complex and varied behaviour of biological membranes and its function.
Download or read book Molecular Dynamics Simulation Studies of Interaction of Amphiphilic Molecules with Lipid Bilayers written by Jieqiong Lin and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book How Solid Substrates Affect a Lipid Bilayer written by Chenyue Xing and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: We use Molecular Dynamics (MD) simulations to investigate how solid substrates interact with a dipalmitoylphosphatidylcholine (DPPC) lipid bilayer and how substrates affect the lipid membrane structurally and dynamically. Supported lipid bilayers are extensively used in experiments as a simplified model for cell membranes. Few simulations of supported bilayers have been performed. We use the MARTINI coarse-grained model to study the supported bilayer computationally. When a lipid bilayer is deposited on the solid substrate, the undulation of the proximal leaflet is suppressed to a higher extent than that of the distal leaflet. Properties of the bilayer including density profiles and lateral mobility exhibit heterogeneity. The proximal leaflet is ordered under the influence of a smooth surface, while the distal leaflet remains the similar to the leaflets in a free-standing bilayer. The lateral pressure profile of the supported bilayer is also different from that of a free-standing bilayer. Membrane proteins undergo undesired conformational changes due to the change in the lateral pressure profile. We study in particular the high local pressure in the proximal leaflet and estimate the interfacial energy associated with it. The interfacial energy falls in the range of activation energy barriers of the large mechanosensative channel (MscL) and may contribute to the opening of MscL without external pressure. Experiencing the strong inwards tension, the proximal leaflet prefers a smaller area per molecule than the distal leaflet and free-standing bilayers. We employ the umbrella sampling technique to calculate the potential of mean force (PMF) of lipid translocation. The free energy difference given by the PMF of various supported bilayer systems indicate that the proximal leaflet needs more lipids than the distal leaflet. The equilibrium density imbalance between two leaflets in the supported bilayer is roughly 4-7%. In addition, the equilibrium area per molecule of the proximal leaflet is estimated to be around 58 Å2, about 4 Å2 smaller than that of the free-standing bilayer. The lipid flip-flop rate in a supported bilayer with the same number of lipids in both leaflets is higher than in the free-standing bilayer, because the energy barrier of flip-flop is lowered by a few kBT.
Download or read book Understanding Lipid Membranes Interactions with Small Molecules and Cholesterol Using Molecular Dynamics Computer Simulations written by Nihit Pokhrel and published by . This book was released on 2019 with total page 88 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular membranes are made up of phospholipids, proteins and cholesterol. The packing of components within the membrane gives rise to important biological phenomena. Understanding these interactions is the most critical step towards predicting membrane behavior. In this dissertation, I focus on lipid bilayer interactions with various molecules. At biologically relevant scale, we investigate how phospholipids interact with small molecules like amino acid residues and cholesterol. At field scale, we study the structure and dynamics of lipid molecules as they bind with clay minerals. I utilize molecular dynamics simulation, both equilibrium and biased, at both coarse-grained and atomistic level to study how these interactions impact membrane thermodynamic properties. I first study membrane permeation by evaluating the efficiency of different computational methods to sample the configurational space of various amino acid and lipid membranes. I show that replica exchange umbrella sampling out-performs others because of the algorithm's ability to sample transition state. Using this method, I calculate cholesterol chemical potential in seven binary lipid membranes. These results demonstrate the sensitivity of the cholesterol chemical potential to the lipid tail unsaturation only if the difference in tail saturation is big, and show that cholesterol has the greatest affinity to saturated PC lipids. These studies provide practical guidance for studying membrane permeation and yield important insight into the thermodynamic properties of lipid bilayer systems. This work will also contribute towards the understanding of cholesterol's effect of membranes, which is a vast and still ongoing field of research. Finally, this research also sheds lights on soil water repellency at the molecular scale. I investigate structural properties of organic matter that are found in soil and find that zwitterionic lipid aggregates bind to the surface of the clay. In this relatively new field, such molecular simulations will have significant scientific impact.
Download or read book Free Energy Calculations written by Christophe Chipot and published by Springer Science & Business Media. This book was released on 2007-01-08 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Lipid Bilayer polypeptide Interactions Studied by Molecular Dynamics Simulation written by Olle Edholm and published by . This book was released on 1985 with total page 34 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Using Molecular Dynamics Simulations and Statistical Modeling to Explore Membrane Structure and Membrane protein Interactions written by Shushan He and published by . This book was released on 2018 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt: The structure of cellular membranes gives rise to important biological phenomena, and understanding the (de)mixing behavior of multicomponent lipid bilayers is an important step toward unraveling the nature of spatial composition heterogeneities in cellular membranes and their role in biological function. In this dissertation we focus on the spatial organization and compositional heterogeneity of model membrane systems and their interaction with small, biologically relevant peptides. I employed both coarse-grained and atomistic molecular dynamics simulations to study the composition phase diagram of a quaternary mixture of phospholipids and cholesterol, as well as to sample the configurational space of peptide-membrane interactions. I investigate the mechanisms controlling membrane spatial heterogeneity and membrane protein interaction. This work yields important new insight into both the structural properties of lipid bilayer systems with spatial and compositional heterogeneity at vastly different length scales, which has prompted numerous publications in the field seeking for a plausible mechanism. This work will also provide perspectives on configurations of the PAP248-286 peptide upon interacting with membranes, which, despite its importance for human health, has not received as much attention from the research community as other amyloid-forming peptides. In this wide-open field such simulations will have significant scientific impact.
Download or read book Molecular Dynamics Studies of Lipid Monolayer and Bilayer Systems written by Bin Liu and published by . This book was released on 2016 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lipids are a crucial ingredient of biomembranes in cells, and they play a pivotal role in many chemical and biological processes. Lipid based structures, such as lipid monolayers and lipid bilayers, both natural and artificial, are gaining their importance and popularity in drug delivery. In this thesis, our main interest is on using molecular modeling and atomistic molecular dynamics simulations to study lipid monolayers and bilayers, and their physical properties and interactions with an antibiotic molecule called daptomycin. This thesis is composed of the research results from two projects. The first project focuses on an atomistic molecular dynamcis study of lipid Langmuir monolayers composed of both pure zwitterionic dipalmitoylphosphatidylcholine (DPPC) and a mixture of DPPC and cationic cetyltrimethylammonium bromide (CTAB). The cationic CTAB lipids have been found to have significant condensing effect on the DPPC / CTAB monolayers, i.e., at the same surface tension or surface pressure, monolayers with higher CTAB molar fraction have smaller area per lipid. With this condensing effect, the DPPC / CTAB monolayers are also able to achieve negative surface tension without introducing buckling into the monolayer structure. The condensing effect is caused by the interplay between the cationic CTAB headgroups and the zwitterionic phosphatidylcholine (PC) headgroups which has electrostatic origin. Moreover, detailed analysis of the structural properties of the monolayers, such as the density profile analysis, hydrogen bonding analysis, chain order parameter calculations and radial distribution function calculations were also performed for better understanding of cationic DPPC/CTAB monolayers. A chapter is dedicated to the discussion of the mean and Gaussian curvatures of the pure DPPC and DPPC/CTAB mixture monolayers. In the second project, MD simulations were employed to study the atomistic details of the antimicrobial activities of daptomycin, a cyclic anionic lipopeptide which treats infections caused by Gram-positive bacteria, with emphasis on its interactions with a model bacteria membrane. Despite having itself a net negative charge, it is selective against negatively charged bacterial membranes. It has been established that daptomycin's antibiotic activity is based on targeting the bacterial membranes and that this antibacterial activity depends on calcium ions. Importantly, however, both the precise role of ions and the physical mechanisms responsible for daptomy-cin's action remain poorly understood. We investigate these issues using three types of molecular dynamics simulations: free energy calculations for a single daptomycin, unbiased simulations for daptomycin tetramers and micellation of daptomycin both in the absence and presence of calcium ions.
