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Molecular Dynamics Approach (molecular + dynamics_approach)
Selected AbstractsMechanical Characterization of Motor Proteins: A Molecular Dynamics ApproachMACROMOLECULAR THEORY AND SIMULATIONS, Issue 7-8 2008Iuliana Aprodu Abstract A new approach, based on molecular dynamics, is presented to measure the mechanical properties of motor proteins, which are important for accomplishing their intracellular functions. Two different set-ups were designed to mimic the optical tweezers and surface force apparatus experiments. The results obtained show that the stiffness and elastic modulus of kinesin motor domain are 377 pN,·,nm,1 and 0.17 GPa, respectively, while the myosin motor domain is characterized by a stiffness of 271 pN,·,nm,1 and an elastic modulus of 0.26 GPa. These results suggest that the source of the very low stiffness detected for full-length molecules is located outside of the globular part of the proteins. [source] Mapping the Druggable Allosteric Space of G-Protein Coupled Receptors: a Fragment-Based Molecular Dynamics ApproachCHEMICAL BIOLOGY & DRUG DESIGN, Issue 3 2010Anthony Ivetac To address the problem of specificity in G-protein coupled receptor (GPCR) drug discovery, there has been tremendous recent interest in allosteric drugs that bind at sites topographically distinct from the orthosteric site. Unfortunately, structure-based drug design of allosteric GPCR ligands has been frustrated by the paucity of structural data for allosteric binding sites, making a strong case for predictive computational methods. In this work, we map the surfaces of the ,1 (,1AR) and ,2 (,2AR) adrenergic receptor structures to detect a series of five potentially druggable allosteric sites. We employ the FTMAP algorithm to identify ,hot spots' with affinity for a variety of organic probe molecules corresponding to drug fragments. Our work is distinguished by an ensemble-based approach, whereby we map diverse receptor conformations taken from molecular dynamics (MD) simulations totaling approximately 0.5 ,s. Our results reveal distinct pockets formed at both solvent-exposed and lipid-exposed cavities, which we interpret in light of experimental data and which may constitute novel targets for GPCR drug discovery. This mapping data can now serve to drive a combination of fragment-based and virtual screening approaches for the discovery of small molecules that bind at these sites and which may offer highly selective therapies. [source] Preface: phys. stat. sol. (b) 245/3PHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 3 2008Christopher W. Smith This is the third Special Issue of physica status solidi (b) focusing on materials with a negative Poisson's ratio or other ,anomalous' physical properties. This issue contains selected papers from the First International Conference on Auxetics and Anomalous Systems held at the University of Exeter, UK, on 4,6 September 2006. Around 50 participants from all over the world as well as from a wide range of scientific and engineering disciplines contributed to what was a highly successful conference. This conference follows in the footsteps of two previous workshops held at the Mathematical Research and Conference Centre in B,dlewo near Pozna,, Poland, in 2004 and 2005 [1, 2]. The papers selected for this issue publish recent results obtained for ,anomalous systems' in experiment, theory and computer simulations. In the following we summarize very briefly their contents. Alderson and Coenen compare the performance of auxetic composites to similar systems with conventional positive Poisson's ratios. They find that there are indeed differences which appear to arise from the change of the overall Poisson's ratio of the composite, some beneficial like a rise in impact tolerance at low impact rates, and others deleterious such as the reduced tolerance at higher impact rates. This is one of the first investigations of possible applications for auxetic materials. The two papers by Gaspar and Koenders both examine the effects of disorder upon anomalous properties, especially negative Poisson's ratio. In the first one Gaspar demonstrates how a mean strain estimate fails to predict negative values of Poisson's ratio because of an inability to account for local fluctuations in elastic properties. For instance it is shown that the volume fraction of auxetic regions in an globally auxetic material (measured experimentally) are smaller than a mean strain homogenisation would require. Koenders and Gaspar explore the elastic properties, and especially Poisson's ratio, of a heterogeneous 2D network of bending beams. They predict auxetic behaviour arising from localised disorder in the packing, and therefore effective locally aggregated elastic properties of the beams. In the three articles by Gatt et al. and Grima et al. models based on simple geometry are used to explain the behaviour of seemingly disparate systems, i.e. 2D honeycombs systems and zeolite SiO2 networks. Two papers concerning honeycombs demonstrate relationships between elastic properties and structure and the bounds for auxetic behaviour. The paper concerning the zeolite Natrolite uses numerical force field based energy minimisation methods to simulate the response of this particular zeolite to applied forces and then simplifies the predicted properties even further by considering structural units as rigid 2D polyhedra linked by flexible hinges. In a similar vein, though using a different approach and concerning a very different form of matter, Heyes shows how the heterogeneity in an assembly of particles in a liquid can affect the elastic properties of a liquid and notably the infinite frequency Poisson's ratio. Heyes uses the Molecular Dynamics approach to simulate a Lennard,Jones fluid under various pressures, notably comparing behaviour under positive and negative pressures. In their first paper Jasiukiewicz and co-authors derive elastic constants of 2D crystals for all four classes of 2D crystalline solids: hexagonal (isotropic), quadratic, rectangular, and oblique systems. In their second paper they demonstrate conditions required for auxetic behaviour of 2D crystals. Auxetic solids are further divided into those with some negative Poisson's ratios (auxetic), all negative Poisson's ratios (completely auxetic) and no negative Poisson's ratios (non-auxetic). Lakes and Wojciechowski consider counterintuitive properties of matter, like negative compressibility, negative Poisson's ratio, negative thermal expansion, negative specific heat, and negative pressure. They present and interpret experimental observations of negative bulk modulus in pre-strained foams. They propose also a constrained microscopic model which exhibits negative compressibility. Finally, they solve a very simple thermodynamic model with negative thermal expansion. Martin et al. take a long stride toward a real world application of auxetic materials with a wide ranging study starting with numerical modelling of a wingbox section to experimental testing in a wind tunnel. They show that an auxetic core in a wing box section can allow a passive aero-elastic response which can be tailored by careful design of the core so that camber, and thus drag, is reduced with increasing airspeed but without sacrificing structural integrity. Miller et al. consider another anomalous physical property, negative thermal expansivity, and its application in the form of particulate composites for amelioration of stresses arising from thermal mismatch. They show via experiments that particles with a negative coefficient of thermal expansion may be used as a composite reinforcer to reduce overall thermal expansion and behave according to the standard volume fraction based models. Narojczyk and Wojciechowski examine the effects of disorder upon the bulk elastic properties of 3D fcc soft sphere systems in terms of particle size. Systems, such as colloids, can be thought of in such terms. The study shows that higher order moments of probability distribution do not influence the bulk elastic properties much, but that lower moments such as the standard deviation of particle size influence the elastic properties greatly. The "hardness" of the particle interaction potential is also important in this context. In general, it is shown that the effect of increasing polydispersity is to increase the Poisson's ratio, except the [110] [10] directions. Scarpa and Malischewsky in their paper on Rayleigh waves in auxetic materials show how the Rayleigh wave speed is affected by the Poisson's ratio. The behaviour is complex and depends upon the homogeneity within the material, for instance slowing with decreasing Poisson's ratio in isotropic solids, but showing the reverse trend and increased sensitivity to Poisson's ratio in laminate composites. Scarpa et al. explore the buckling behaviour of auxetic tubes via three types of model, a simple beam mechanics and Eulerian buckling model, a 3D linear elastic FE model and a bespoke non-linear continuum model. The more sophisticated models provide increasing insight into the buckling behaviour though the simple beam model predicts reasonably well in the pre-buckling linear region. Some unexpected and interesting behaviour is predicted by the continuum model as the Poisson's ratio approaches the isotropic limit of ,1, including increasing sensitivity to Poisson's ratio and rapid mode jumping between integer wave numbers. The paper by Shilko et al. presents an analysis of a particular kind of friction joint, a double lap joint, and explores the effects of altering the elastic properties of one component, in particular it's Poisson's ratio. The manuscript introduces the evolution of smart materials from monolithic materials, and the classification of composites exhibiting negative Poisson's ratios. The paper then presents the case of a double lap joint and performs a sensitivity type study, via a 2D FE model, of the effects of changing the elastic properties and degree of anisotropy of one section of the model on various parameters defining the limits of functionality of the joint. The main finding is that an enhanced shear modulus, via a negative Poisson's ratio, can endow such a friction joint with superior performance. Manufacturing of auxetic materials on a commercial scale has proved to be the largest obstacle to their fuller exploitation. The paper by Simkins et al. explores one route for post processing of auxetic polymers fibres produced by a conventional melt extrusion route. Simkins et al. showed that a post process thermal annealing treatment, with carefully optimised parameters, was able to even out otherwise inhomogenous auxetic properties, and moreover improve other elastic and fracture properties often sacrificed for auxetic behaviour. We gratefully acknowledge the support given by the sponsors of the conference, namely the EPSRC of the UK and Auxetic Technologies Ltd. (UK). We also thank the Scientific Committee, the Organising Committee, and all the participants of the conference. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Simulation of DNA electrophoresis in systems of large number of solvent particles by coarse-grained hybrid molecular dynamics approachJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 4 2009Rong Wang Abstract Simulation of DNA electrophoresis facilitates the design of DNA separation devices. Various methods have been explored for simulating DNA electrophoresis and other processes using implicit and explicit solvent models. Explicit solvent models are highly desired but their applications may be limited by high computing cost in simulating large number of solvent particles. In this work, a coarse-grained hybrid molecular dynamics (CGH-MD) approach was introduced for simulating DNA electrophoresis in explicit solvent of large number of solvent particles. CGH-MD was tested in the simulation of a polymer solution and computation of nonuniform charge distribution in a cylindrical nanotube, which shows good agreement with observations and those of more rigorous computational methods at a significantly lower computing cost than other explicit-solvent methods. CGH-MD was further applied to the simulation of DNA electrophoresis in a polymer solution and in a well-studied nanofluidic device. Simulation results are consistent with observations and reported simulation results, suggesting that CGH-MD is potentially useful for studying electrophoresis of macromolecules and assemblies in nanofluidic, microfluidic, and microstructure array systems that involve extremely large number of solvent particles, nonuniformly distributed electrostatic interactions, bound and sequestered water molecules. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009 [source] Direct Assignment of Enantiofacial Discrimination on Single Heterocyclic Substrates by Self-induced CDCHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2005Carsten Siering Abstract The first direct assignment of highly dynamic enantiofacial discrimination acting on a single heterocyclic substrate has been achieved by a combination of experimental and theoretical CD spectroscopy. The interaction of chirally modified hosts based on triphenylene ketals with appropriate prochiral guests can lead to the preferential formation of one diastereomeric host,guest complex. This reversible stereoselective binding transmits the chiral information from remote chiral groups in the host to the strongly absorbing triphenylene chromophore, which gives rise to self-induced CD. This effect was exploited for the determination of the enantiofacial recognition in various host,guest systems. Inversion of the steric demand either of the chiral substituents at the host or of the prochiral guest leads to almost complete inversion of the resulting CD spectra. For the assignment of the absolute stereochemistry of the complexes, a combined molecular dynamics/quantum-chemical approach was successfully employed. Despite the size and the highly dynamic character of the supramolecular systems, fundamental properties of the systems and details of the spectra were simulated accurately, providing access to fast and reliable assignment of the enantiofacial preference. The results are highly consistent with available X-ray data. [source] | ||||||||||