Coarse-grained (CG) models provide a computationally efficient method for rapidly investigating the long time- and length-scale processes that play critical role in many important biological soft matter processes. Recently, Izvekov Voth introduced new multiscale coarse-graining (MS-CG) [J. Phys. Chem. B 109, 2469 (2005); J. 123, 134105 (2005)] determining effective interactions between CG sites using information from simulations of atomically detailed models. The present work develops formal...

The multiscale coarse-graining (MS-CG) method [S. Izvekov and G. A. Voth, J. Phys. Chem. B 109, 2469 (2005); 123, 134105 (2005)] employs a variational principle to determine an interaction potential for CG model from simulations of atomically detailed the same system. companion paper proved that, if no restrictions regarding form are introduced equilibrium distribution atomistic has been adequately sampled, then MS-CG determines exact many-body mean force (PMF) governing sites generated by...

Many enzymes mold their structures to enclose substrates in active sites such that conformational remodeling may be required during each catalytic cycle. In adenylate kinase (AK), this involves a large-amplitude rearrangement of the enzyme's lid domain. Using our method high-resolution single-molecule FRET, we directly followed AK's domain movements on its time scale. To quantitatively measure entire distribution, have applied maximum entropy-based methods remove photon-counting noise from...

A statistical mechanical framework elucidates the significance of structural correlations between coarse-grained (CG) sites in multiscale coarse-graining (MS-CG) method (Izvekov, S.; Voth, G. A. J. Phys. Chem. B 2005, 109, 2469; 123, 134105). If no approximations are made, then MS-CG yields a many-body multidimensional potential mean force describing interactions CG sites. However, numerical applications typically employ set pair potentials to describe nonbonded interactions. The analogy and...

The structural and mechanical properties of monomeric actin (G-actin), the trimer nucleus, filaments (F-actins) are determined as a function conformation DNase I-binding loop (DB loop) by using all-atom molecular dynamics simulations coarse-grained (CG) analysis. Recent x-ray structures ADP-bound G-actin (G-ADP) Otterbein et al. [Otterbein, L. R., Graceffa, P. & Dominguez, R. (2001) Science 293, 708–711] ATP-bound (G-ATP) Graceffa Dominguez [Graceffa, (2003) J. Biol. Chem. 278,...

Pretreatment for deconstructing the multifaceted interaction network in crystalline cellulose is a limiting step making fuels from lignocellulosic biomass. Not soluble water and most organic solvents, was found to dissolve certain classes of ionic liquids (ILs). To elucidate underlying mechanisms, we simulated deconstruction by peeling off an 11-residue glucan chain microfibril computed free-energy profile 1-butyl-3-methylimidazolium chloride (BmimCl) IL. For this process, calculated...

Biomass recalcitrance is a fundamental bottleneck to producing fuels from renewable sources. To understand its molecular origin, we characterize the interaction network and solvation structures of cellulose microfibrils via all-atom dynamics simulations. The divided into three components: intrachain, interchain, intersheet interactions. Analysis their spatial dependence energetics indicate that interactions are most robust strongest component do not display noticeable on solvent exposure....

Abstract A double-negative feedback loop formed by the morning genes CIRCADIAN CLOCK ASSOCIATED1 ( CCA1 )/ LATE ELONGATED HYPOCOTYL LHY ) and evening gene TIMING OF CAB EXPRESSION1 TOC1 contributes to regulation of circadian clock in Arabidopsis . 24-h cycle starts with peak expression at dawn. Although is targeted multiple transcriptional repressors, including PSEUDO-RESPONSE REGULATOR9 (PRR9), PRR7, PRR5 HIKING EXPEDITION (CHE), activators remain elusive. Here we use mathematical modelling...

Abstract The exonuclease activity of Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for processing matched/mismatched terminus in various DNA repair pathways and removing nucleoside analogs associated with drug resistance. To fill the gap structural basis exonucleolytic cleavage, we determine APE1-dsDNA complex structures displaying end-binding. As an exonuclease, APE1 does not show base preference but can distinguish dsDNAs different features. Integration assaying enzyme binding...

In this article, we present a superlinear minimization scheme for the nudged elastic band (NEB) method, which determines minimum-energy path (MEP) of reaction via connecting intermediate “replicas” between reactant and product. The is based on quasi-Newton method: adopted basis Newton–Raphson (ABNR) scheme. each step ABNR minimization, procedure performed in subspace user-defined dimension. tangent directions at new are determined self-consistently subspace. acceleration proposed over...

Cellulose is present in biomass as crystalline microfibrils held together by a complex network of intermolecular interactions making it difficult to initiate its hydrolysis and conversion fuels. While cellulose insoluble water most organic solvents, complete dissolution can be achieved certain classes ionic liquids (ILs). The study was undertaken analyze the thermodynamic driving forces this process understand how anions cations comprising an IL interact with different moieties glucose...

The mechanism of oxidation organic sulfides in aqueous solutions by hydrogen peroxide was investigated via ab initio calculations. Specifically, two reactions, transfer to form water oxide and the dimethyl sulfide (DMS) sulfoxide, were studied as models these processes general. Solvent effects are included both including explicitly molecules polarizable continuum model. former found have a much more significant effect than latter. When explicit included, different from those proposed...

Two new approaches are presented for obtaining coarse-grained (CG) force fields from atomistic molecular dynamics (MD) trajectories. The first approach is the force-matching (FM) method whereby data obtained an explicit MD simulation utilized to determine CG fields. performance of FM demonstrated by applying it derive a model dimyristoylphosphatidylcholine (DMPC) lipid bilayer. second fluctuation-matching fluctuations specific internal coordinates extracted simulations field. fluctuation...

Three multiscale computational methodologies for biomolecular systems are described: the force-matching method developing coarse-grained models directly from atomistic simulations; quasi-particle approach of simulating field theory representations at mesoscopic scale; and multiscale-coupling direct information transfer between scales on fly. The statistical mechanical background each methods is described in a comprehensive manner order to highlight their theoretical foundations. Examples...

A new multiscale coarse-graining (CG) methodology is developed to bridge molecular and hydrodynamic models of a fluid. The representation considered in this work based on the equations fluctuating hydrodynamics (FH). essence method mapping from position velocity vectors snapshot dynamics (MD) simulation field variables Eulerian cells representation. By explicit consideration effective lengthscale d(mol) that characterizes volume molecule, computed density fluctuations MD via our procedure...

The entropic driving forces of cellulose dissolution in water and the ionic liquid 1-butyl-3-methylimidazolium chloride (BmimCl) are investigated via molecular dynamics simulations two-phase thermodynamic model. An atomistic model was simulated at a dissociated state microfibril to represent dissolution. calculated values entropy internal energy changes between two states inform interplay energetic In both BmimCl, we found that associated with solvent degrees freedom (DOF) decreases upon...

In higher plants (e.g., Arabidopsis thaliana), the core structure of circadian clock is mostly governed by a repression process with very few direct activators. With series simplified models, we studied underlying mechanism and found that consists type-2 incoherent feed-forward loops (IFFLs), one them creating pulse-like expression in PRR9/7. The double-negative feedback loop between CCA1/LHY PRR5/TOC1 generates bistable, hysteretic behavior clock. We IFFL involving PRR9/7 breaks bistability...

We develop a new method to invert the target profiles of radial distribution functions (RDFs) pair forces between particles. The RDFs can be obtained from all-atom molecular dynamics (MD) simulations or experiments and inverted used in at coarse-grained (CG) scale. Our is based on variational principle that determines mean CG sites after integrating out unwanted degrees freedom. solution this has been shown correspond Yvon-Born-Green (YBG) equation [Noid et al., J. Phys. Chem. B 111, 4116...