Multipolar Force Fields for Amide-I Spectroscopy from Conformational Dynamics of the Alanine-Trimer

The dynamics and spectroscopy of N-methyl-acetamide (NMA) and trialanine in solution is characterized from molecular dynamics (MD) simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1-d infrared spectra, the frequency splitting between the two amide-I groups is 10 cm$^{-1}$ from the PC, 13 cm$^{-1}$ from the MTP, and 47 cm$^{-1}$ from SCC-DFTB simulations, compared with 25 cm$^{-1}$ from experiment. The frequency trajectory required for determining the frequency fluctuation correlation function (FFCF) is determined from individual (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCF $C(t=0)$, and the static component $\Delta_0^2$ from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)$_3$. Contrary to that, for the analysis excluding mode-mode coupling (INM) the FFCF decays to zero too rapidly and for simulations with a PC-based force field the $\Delta_0^2$ is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature , whereas that covered by the MTP-based simulations is dominated by P$_{\rm II}$ which agrees with and confirms recently reported, Bayesian-refined populations based on 1-dimensional infrared experiments. Full normal mode analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine

Steered molecular dynamics simulations reveal the role of Ca2+ in regulating mechanostability of cellulose-binding proteins

The conversion of cellulosic biomass into biofuels requires degradation of the biomass into fermentable sugars. The most efficient natural cellulase system for carrying out this conversion is an extracellular multi-enzymatic complex named the cellulosome. In addition to temperature and pH stability, mechanical stability is important for functioning of cellulosome domains, and experimental techniques such as Single Molecule Force Spectroscopy (SMFS) have been used to measure the mechanical strength of several cellulosomal proteins. Molecular dynamics computer simulations provide complementary atomic-resolution quantitative maps of domain mechanical stability for identification of experimental leads for protein stabilization. In this study, we used multi-scale steered molecular dynamics computer simulations, benchmarked against new SMFS measurements, to measure the intermolecular contacts that confer high mechanical stability to a family 3 Carbohydrate Binding Module protein (CBM3) derived from the archetypal Clostridium thermocellum cellulosome. Our data predicts that electrostatic interactions in the calcium binding pocket modulate the mechanostability of the cellulose-binding module, which provides an additional design rule for the rational re-engineering of designer cellulosomes for biotechnology. Our data offers new molecular insights into the origins of mechanostability in cellulose binding domains and gives leads for synthesis of more robust cellulose-binding protein modules. On the other hand, simulations predict that insertion of a flexible strand can promote alternative unfolding pathways and dramatically reduce the mechanostability of the carbohydrate binding module, which gives routes to rational design of tailormade fingerprint complexes for force spectroscopy experiments

Coupled protein-ligand dynamics in truncated hemoglobin N from atomistic simulations and transition networks

The nature of ligand motion in proteins is difficult to characterize directly using experiment. Specifically, it is unclear to what degree these motions are coupled.; All-atom simulations are used to sample ligand motion in truncated Hemoglobin N. A transition network analysis including ligand- and protein-degrees of freedom is used to analyze the microscopic dynamics.; Clustering of two different subsets of MD trajectories highlights the importance of a diverse and exhaustive description to define the macrostates for a ligand-migration network. Monte Carlo simulations on the transition matrices from one particular clustering are able to faithfully capture the atomistic simulations. Contrary to clustering by ligand positions only, including a protein degree of freedom yields considerably improved coarse grained dynamics. Analysis with and without imposing detailed balance agree closely which suggests that the underlying atomistic simulations are converged with respect to sampling transitions between neighboring sites.; Protein and ligand dynamics are not independent from each other and ligand migration through globular proteins is not passive diffusion.; Transition network analysis is a powerful tool to analyze and characterize the microscopic dynamics in complex systems. This article is part of a Special Issue entitled Recent developments of molecular dynamics

Structure and Dynamics of an Electrolyte Confined in Charged Nanopores

International audienceMolecular Dynamics simulations are used to investigate the structure and dynamics of an aqueous electrolyte (NaCl) confined within a nanomembrane, which consists of a nanopore with a diameter 3 nm having a negatively charged surface. Both nanomembranes with a diffuse charge and with local charges are considered (in both cases, two surface charge densities are considered, -0.9 e/nm(2) and -1.8 e/nm(2)). For all nanomembranes, significant layering of water and ions in the vicinity of the nanomembrane surface is observed. While the distribution of water and chloride ions is nearly insensitive to the nanomembrane charge and type, the arrangement of sodium cations within the nanomembrane depends on the system being considered. The water and ion density profiles in the nanomembranes are compared with the predictions of a modified Poisson-Boltzmann equation in which charge image, solvation effects, and dispersion interactions with the surface are taken into account [Huang et al. Langmuir, 2008, 24, 1442]. The self-diffusion coefficient for a given species is smaller than its bulk counterpart and is at most 75% of the bulk value. While the self-diffusion coefficients for water and sodium cations decrease with decreasing the overall negative charge of the nanomembrane, the self-diffusion coefficient for the chloride anions is nearly independent of the nanomembrane type and charge. We also estimate the dynamics of the confined aqueous electrolyte by calculating time correlation functions which allow estimating solvation, ion pairing, and residence times

Interactions chromophore-substrat dans les matériaux hybrides (approche spectroscopique expérimentale et théorique)

Ce travail est une approche associant la caractérisation par spectroscopie UV-visible et la modélisation en chimie quantique et en dynamique moléculaire classique pour l étude de la photodynamique des matériaux hybrides. Il a permis l interprétation de l ensemble du spectre d absorption du 9,10-dicyanoanthracène (DCA), ainsi que la formation d un agrégat présentant deux conformations. Un examen appronfondi des spectres de fluorescence des matériaux hybrides fortement dopés en colorant met en évidence les limites de cette technique artéfacts de fluorescence pour des échantillons optiquement épais. L étude du dimère de DCA par recuits simulés en dynamique moléculaire classique, confirme l existence de seulement deux conformations pour cette espèce dans le vide. Le calcul du potentiel de force moyenne, qui donne accès à l énergie libre de dissociation du dimère, indique des stabilités relatives en solution en bon accord avec les données expérimentales. Ce travail a permis la mise au point d un modèle du DCA et d un champ de forces décrivant une silice hydrophobe. Des développements dans le code DL_POLY ont en outre été réalisés, tels que la décomposition de l énergie totale du système en contributions propres à chaque sous-sytème, la simulation d une transition électronique et le calcul de l énergie libre au moyen de l intégration thermodynamique.The developpement of the applications of hybrid materials implies the use of specific technics and tools to study and understand the behaviors and the mecanisms that occure in these materials. We combined optical spectroscopy and molecular modeling by both quantum mechanics and classical molecular dynamics. We identify the whole absorption spectrum of 9,10-dicyanoanthracene (DCA) and show the aggregation of DCA on silica, with two conformations. We underline the limitations of optical spectroscopy, through the fluoresecence artefacts, for optically thick samples. A molecular dynamics force field for the DCA is developed and a model is provided for pure hydrophobic silica. The study of the dimer of DCA by simulated annealing confirmes the existence of only two conformations for this dimer in vacuum. The calculation of the potential of mean force, that provides the free energy of dissociation, gives results in relatively good agreement with experiments for the stability of the dimer. Finally, we developed new features in the DL_POLY code for the breaking down of the total energy in contributions from each subsystem, the simulation of electronic transitions and the calculation of the free energy via thermodynamic integration.PAU-BU Sciences (644452103) / SudocSudocFranceF

Host and adsorbate dynamics in silicates with flexible frameworks: Empirical force field simulation of water in silicalite.

International audienceMol. dynamics simulations are performed on the pure silica zeolite silicalite (MFI framework code), maintaining via a new force field both framework flexibility and realistic account of electrostatic interactions with adsorbed water. The force field is similar to the well-known "BKS" model, but with reduced partial at. charges and reoptimized covalent bond potential wells. The present force field reproduces the monoclinic to orthorhombic transition of silicalite. The force field correctly represents the hydrophobicity of pure silica silicalite, both the adsorption energy, and the mol. diffusion consts. of water. Two types of adsorption, specific and weak unspecific, are predicted on the channel walls and at the channel intersection. We discuss mol. diffusion of water in silicalite, deducing a barrier to crossing between the straight and the zigzag channels. Anal. of the thermal motion shows that at room temp., framework oxygen atoms incurring into the zeolite channels significantly influence the dynamics of adsorbed wate