Direct comparisons of experimental and calculated neutron structure factors of pure solvents as a method for force field validation.
ABSTRACT: In the present letter, we directly compare neutron structure factors calculated from force field (FF)-based molecular dynamics simulations with experimental structure factors for water, methanol, and tetrahydrofuran (THF). For water, the difference in the measured structure factors is more significant than differences between the FFs. It is shown that the inclusion of electronic polarization in the force field improves the agreement with experiment for the more-polar methanol, whereas the results are comparable for the additive and polarizable FF models of the less-polar THF. The data presented here confirm that comparing the calculated scattering profiles from FF-based MD simulations to measured neutron structure factors is a promising method for FF validation and development.
Project description:In this paper, we studied the aggregation of amphiphilic polymer epoxy-terminated polydimethylsiloxane (PDMS-E) grafted gelatin (PGG) in water induced by methanol, ethanol, 2-propanol, acetone, tetrahydrofuran (THF), and 1,4-dioxane. The aggregation pattern of the polymer was monitored by infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and scanning electron microscopy. It was revealed that the aggregate morphology showed clear dependence on the solvent polarity. The PGG aggregates had regular spherical morphology in polar solvents, including water, methanol, ethanol, 2-propanol, and acetone. The coating performance was evaluated by X-ray photoelectron spectroscopy and friction experiment, and PGG and acetone coating exhibited excellent coating performance on the surface of pigskin. Gel was formed in acetone and tetrahydrofuran (THF) with the slow evaporation of solvent, and this property can possibly be applied to industrial sewage treatment. White precipitate and soft film were formed in non-polar 1,4-dioxane.
Project description:Clay minerals are ubiquitous in nature, and the manner in which they interact with their surroundings has important industrial and environmental implications. Consequently, a molecular-level understanding of the adsorption of molecules on clay surfaces is crucial. In this regard computer simulations play an important role, yet the accuracy of widely used empirical force fields (FF) and density functional theory (DFT) exchange-correlation functionals is often unclear in adsorption systems dominated by weak interactions. Herein we present results from quantum Monte Carlo (QMC) for water and methanol adsorption on the prototypical clay kaolinite. To the best of our knowledge, this is the first time QMC has been used to investigate adsorption at a complex, natural surface such as a clay. As well as being valuable in their own right, the QMC benchmarks obtained provide reference data against which the performance of cheaper DFT methods can be tested. Indeed using various DFT exchange-correlation functionals yields a very broad range of adsorption energies, and it is unclear a priori which evaluation is better. QMC reveals that in the systems considered here it is essential to account for van der Waals (vdW) dispersion forces since this alters both the absolute and relative adsorption energies of water and methanol. We show, via FF simulations, that incorrect relative energies can lead to significant changes in the interfacial densities of water and methanol solutions at the kaolinite interface. Despite the clear improvements offered by the vdW-corrected and the vdW-inclusive functionals, absolute adsorption energies are often overestimated, suggesting that the treatment of vdW forces in DFT is not yet a solved problem.
Project description:A significant modification to the additive all-atom CHARMM lipid force field (FF) is developed and applied to phospholipid bilayers with both choline and ethanolamine containing head groups and with both saturated and unsaturated aliphatic chains. Motivated by the current CHARMM lipid FF (C27 and C27r) systematically yielding values of the surface area per lipid that are smaller than experimental estimates and gel-like structures of bilayers well above the gel transition temperature, selected torsional, Lennard-Jones and partial atomic charge parameters were modified by targeting both quantum mechanical (QM) and experimental data. QM calculations ranging from high-level ab initio calculations on small molecules to semiempirical QM studies on a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer in combination with experimental thermodynamic data were used as target data for parameter optimization. These changes were tested with simulations of pure bilayers at high hydration of the following six lipids: DPPC, 1,2-dimyristoyl-sn-phosphatidylcholine (DMPC), 1,2-dilauroyl-sn-phosphatidylcholine (DLPC), 1-palmitoyl-2-oleoyl-sn-phosphatidylcholine (POPC), 1,2-dioleoyl-sn-phosphatidylcholine (DOPC), and 1-palmitoyl-2-oleoyl-sn-phosphatidylethanolamine (POPE); simulations of a low hydration DOPC bilayer were also performed. Agreement with experimental surface area is on average within 2%, and the density profiles agree well with neutron and X-ray diffraction experiments. NMR deuterium order parameters (S(CD)) are well predicted with the new FF, including proper splitting of the S(CD) for the aliphatic carbon adjacent to the carbonyl for DPPC, POPE, and POPC bilayers. The area compressibility modulus and frequency dependence of (13)C NMR relaxation rates of DPPC and the water distribution of low hydration DOPC bilayers also agree well with experiment. Accordingly, the presented lipid FF, referred to as C36, allows for molecular dynamics simulations to be run in the tensionless ensemble (NPT), and is anticipated to be of utility for simulations of pure lipid systems as well as heterogeneous systems including membrane proteins.
Project description:To compare ordered water positions from experiment with those from molecular dynamics (MD) simulations, a number of MD models of water structure in crystalline endoglucanase were calculated. The starting MD model was derived from a joint X-ray and neutron diffraction crystal structure, enabling the use of experimentally assigned protonation states. Simulations were performed in the crystalline state, using a periodic 2 × 2 × 2 supercell with explicit solvent. Water X-ray and neutron scattering density maps were computed from MD trajectories using standard macromolecular crystallography methods. In one set of simulations, harmonic restraints were applied to bias the protein structure toward the crystal structure. For these simulations, the recall of crystallographic waters using strong peaks in the MD water electron density was very good, and there also was substantial visual agreement between the boomerang-like wings of the neutron scattering density and the crystalline water hydrogen positions. An unrestrained simulation also was performed. For this simulation, the recall of crystallographic waters was much lower. For both restrained and unrestrained simulations, the strongest water density peaks were associated with crystallographic waters. The results demonstrate that it is now possible to recover crystallographic water structure using restrained MD simulations but that it is not yet reasonable to expect unrestrained MD simulations to do the same. Further development and generalization of MD water models for force-field development, macromolecular crystallography, and medicinal chemistry applications is now warranted. In particular, the combination of room-temperature crystallography, neutron diffraction, and crystalline MD simulations promises to substantially advance modeling of biomolecular solvation.
Project description:Tenebrio molitor antifreeze protein (TmAFP) was simulated with growing ice-water interfaces at a realistic melting temperature using TIP4P/Ice water model. To test compatibility of protein force fields (FFs) with TIP4P/Ice water, CHARMM, AMBER, and OPLS FFs were applied. CHARMM and AMBER FFs predict more ?-sheet structure and lower diffusivity of TmAFP at the ice-water interface than does OPLS FF, indicating that ?-sheet structure is important for the TmAFP-interface binding and antifreeze activity. In particular, CHARMM FF more clearly distinguishes the strengths of hydrogen bonds in the ice-binding and non-ice-binding sites of TmAFP than do other FFs, in agreement with experiments, implying that CHARMM FF can be a reasonable choice to simulate proteins with TIP4P/Ice water. Simulations of mutated TmAFPs show that for the same density of Thr residues, continuous arrangement of Thr with the distance of 0.4~0.6 nm induces the higher extent of antifreeze activity than does intermittent arrangement of Thr with larger distances. These findings suggest the choice of CHARMM FF for AFP-TIP4P/Ice simulations and help explain the relationship between Thr-residue arrangement and antifreeze activity.
Project description:Self-assembly is a process of key importance in natural systems and in nanotechnology. Peptides are attractive building blocks due to their relative facile synthesis, biocompatibility, and other unique properties. Diphenylalanine (FF) and its derivatives are known to form nanostructures of various architectures and interesting and varied characteristics. The larger triphenylalanine peptide (FFF) was found to self-assemble as efficiently as FF, forming related but distinct architectures of plate-like and spherical nanostructures. Here, to understand the effect of triaromatic systems on the self-assembly process, we examined carboxybenzyl-protected diphenylalanine (z-FF) as a minimal model for such an arrangement. We explored different self-assembly conditions by changing solvent compositions and peptide concentrations, generating a phase diagram for the assemblies. We discovered that z-FF can form a variety of structures, including nanowires, fibers, nanospheres, and nanotoroids, the latter were previously observed only in considerably larger or co-assembly systems. Secondary structure analysis revealed that all assemblies possessed a ?-sheet conformation. Additionally, in solvent combinations with high water ratios, z-FF formed rigid and self-healing hydrogels. X-ray crystallography revealed a "wishbone" structure, in which z-FF dimers are linked by hydrogen bonds mediated by methanol molecules, with a 2-fold screw symmetry along the c-axis. All-atom molecular dynamics (MD) simulations revealed conformations similar to the crystal structure. Coarse-grained MD simulated the assembly of the peptide into either fibers or spheres in different solvent systems, consistent with the experimental results. This work thus expands the building block library for the fabrication of nanostructures by peptide self-assembly.
Project description:Modern chemistry seems to be unlimited in molecular size and elemental composition. Metal-organic frameworks or biological macromolecules involve complex architectures and a large variety of elements. Yet, a general and broadly applicable theoretical method to describe the structures and interactions of molecules beyond the 1000-atom size regime semi-quantitatively is not self-evident. For this purpose, a generic force field named GFN-FF is presented, which is completely newly developed to enable fast structure optimizations and molecular-dynamics simulations for basically any chemical structure consisting of elements up to radon. The freely available computer program requires only starting coordinates and elemental composition as input from which, fully automatically, all potential-energy terms are constructed. GFN-FF outperforms other force fields in terms of generality and accuracy, approaching the performance of much more elaborate quantum-mechanical methods in many cases.
Project description:Protein structure and dynamics can be characterized on the atomistic level with both nuclear magnetic resonance (NMR) experiments and molecular dynamics (MD) simulations. Here, we quantify the ability of the recently presented CHARMM36 (C36) force field (FF) to reproduce various NMR observables using MD simulations. The studied NMR properties include backbone scalar couplings across hydrogen bonds, residual dipolar couplings (RDCs) and relaxation order parameter, as well as scalar couplings, RDCs, and order parameters for side-chain amino- and methyl-containing groups. It is shown that the C36 FF leads to better correlation with experimental data compared to the CHARMM22/CMAP FF and suggest using C36 in protein simulations. Although both CHARMM FFs contains the same nonbond parameters, our results show how the changes in the internal parameters associated with the peptide backbone via CMAP and the ?1 and ?2 dihedral parameters leads to improved treatment of the analyzed nonbond interactions. This highlights the importance of proper treatment of the internal covalent components in modeling nonbond interactions with molecular mechanics FFs.
Project description:Aqueous proline solutions are deceptively simple as they can take on complex roles such as protein chaperones, cryoprotectants, and hydrotropic agents in biological processes. Here, a molecular level picture of proline/water mixtures is developed. Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations of aqueous proline amino acid at the B-LYP level of theory, performed using IBM's Blue Gene/L supercomputer and massively parallel software, reveal hydrogen-bonding propensities that are at odds with the predictions of the CHARMM22 empirical force field but are in better agreement with results of recent neutron diffraction experiments. In general, the CPAIMD (B-LYP) simulations predict a simplified structural model of proline/water mixtures consisting of fewer distinct local motifs. Comparisons of simulation results to experiment are made by direct evaluation of the neutron static structure factor S(Q) from CPAIMD (B-LYP) trajectories as well as to the results of the empirical potential structure refinement reverse Monte Carlo procedure applied to the neutron data.
Project description:We illustrate control of a polarized laser optical trapping potential landscape through the nonideal mixing of binary liquids. The inherent trapping potential asymmetry (ITPA) present in the trapping region results from the asymmetric intensity distribution in focal volume due to the high numerical aperture objective lens. Experimentally, we show that this ITPA effect can be modified and/or removed by the use of binary liquid mixtures. From our femtosecond optical tweezers experiments, we determine the topograph of the trapping potential base on the fluctuation-dissipation theorem. Additionally, the Brownian motion of the trapped bead is sensitive to the frictional force (FF) of the surroundings that is exerted by clusters of water and alcohol binary mixture through extended hydrogen bonding. Thus, using these two effects, ITPA and FF of the medium, we have shown that one can indeed modify the effective trapping potential landscape. Water-alcohol binary mixtures display a nonlinear dependence on the microrheological properties of the solvent composition as a result of rigid cluster formation. Volumetrically, at about 30% methanol in water binary mixture, the trapping asymmetry is minimal. In this particular binary mixture composition, the hydrophobic part of the methanol molecule is surrounded by 'cages' of water molecules. Enhanced H-bonding network of water molecules results in higher viscosity, which contributes to the higher frictional force. Increased viscosity decreases the degree of anisotropy due to hindered dipolar rotation. However, at higher methanol concentrations, the methanol molecules are no longer contained within the water cages and are free to move, which decrease their overall bulk viscosity. Thus, for pure solvents, experimentally measured anisotropy matches quite well with the theoretical prediction, but this fails in case of the binary mixtures due to the increased frictional force exerted by binary mixtures that result from the formation of cage-like structures.