A quantum fluid of metallic hydrogen suggested by first-principles calculations

It is generally assumed that solid hydrogen will transform into a metallic alkali-like crystal at sufficiently high pressure. However, some theoretical models have also suggested that compressed hydrogen may form an unusual two-component (protons and electrons) metallic fluid at low temperature, or possibly even a zero-temperature liquid ground state. The existence of these new states of matter is conditional on the presence of a maximum in the melting temperature versus pressure curve (the 'melt line'). Previous measurements of the hydrogen melt line up to pressures of 44 GPa have led to controversial conclusions regarding the existence of this maximum. Here we report ab initio calculations that establish the melt line up to 200 GPa. We predict that subtle changes in the intermolecular interactions lead to a decline of the melt line above 90 GPa. The implication is that as solid molecular hydrogen is compressed, it transforms into a low-temperature quantum fluid before becoming a monatomic crystal. The emerging low-temperature phase diagram of hydrogen and its isotopes bears analogies with the familiar phases of 3He and 4He, the only known zero-temperature liquids, but the long-range Coulombic interactions and the large component mass ratio present in hydrogen would ensure dramatically different propertiesComment: See related paper: cond-mat/041040

Multiscale Coarse-Graining of the Protein Energy Landscape

A variety of coarse-grained (CG) models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force-matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states

Shock response of single crystal and nanocrystalline pentaerythritol tetranitrate: Implications to hotspot formation in energetic materials

We investigate shock response of single crystal and nanocrystalline pentaerythritol tetranitrate (PETN) with a coarse-grained model and molecular dynamics simulations, as regards mechanical hotspot formation in the absence or presence of grain boundaries (GBs). Single crystals with different orientations, and columnar nanocrystalline PETN with regular hexagonal, irregular hexagonal, and random GB patterns, are subjected to shock loading at different shock strengths. In single crystals, shock-induced plasticity is consistent with resolved shear stress calculations and the steric hindrance model, and this deformation leads to local heating. For regular-shaped hexagonal columnar nanocrystalline PETN, different misorientation angles lead to activation of different/same slip systems, different deformation in individual grains and as a whole, different GB friction, different temperature distributions, and then, different hotspot characteristics. Compared to their regular-shaped hexagonal counterpart, nanocrystalline PETN with irregular hexagonal GB pattern and that with random GBs, show deformation and hotspot features specific to their GBs. Driven by stress concentration, hotspot formation is directly related to GB friction and GB-initiated crystal plasticity, and the exact deformation is dictated by grain orientations and resolved shear stresses. GB friction alone can induce hotspots, but the hotspot temperature can be enhanced if it is coupled with GB-initiated crystal plasticity, and the slip of GB atoms has components out of the GB plane. The magnitude of shearing can correlate well with temperature, but the slip direction of GB atoms relative to GBs may play a critical role. Wave propagation through varying microstructure may also induce differences in stress states (e.g., stress concentrations) and loading rates, and thus, local temperature rise. GB-related friction and plasticity induce local heating or mechanical hotspots, which could be precursors to chemical hotspot formation related to initiation in energetic materials, in the absence of other, likely more effective, means for hotspot formation such as void collapse

PIP2-Binding Site in Kir Channels: Definition by Multiscale Biomolecular Simulations†

Phosphatidylinositol bisphosphate (PIP(2)) is an activator of mammalian inwardly rectifying potassium (Kir) channels. Multiscale simulations, via a sequential combination of coarse-grained and atomistic molecular dynamics, enabled exploration of the interactions of PIP(2) molecules within the inner leaflet of a lipid bilayer membrane with possible binding sites on Kir channels. Three Kir channel structures were investigated: X-ray structures of KirBac1.1 and of a Kir3.1-KirBac1.3 chimera and a homology model of Kir6.2. Coarse-grained simulations of the Kir channels in PIP(2)-containing lipid bilayers identified the PIP(2)-binding site on each channel. These models of the PIP(2)-channel complexes were refined by conversion to an atomistic representation followed by molecular dynamics simulation in a lipid bilayer. All three channels were revealed to contain a conserved binding site at the N-terminal end of the slide (M0) helix, at the interface between adjacent subunits of the channel. This binding site agrees with mutagenesis data and is in the proximity of the site occupied by a detergent molecule in the Kir chimera channel crystal. Polar contacts in the coarse-grained simulations corresponded to long-lived electrostatic and H-bonding interactions between the channel and PIP(2) in the atomistic simulations, enabling identification of key side chains

Combining Optimal Control Theory and Molecular Dynamics for Protein Folding

A new method to develop low-energy folding routes for proteins is presented. The novel aspect of the proposed approach is the synergistic use of optimal control theory with Molecular Dynamics (MD). In the first step of the method, optimal control theory is employed to compute the force field and the optimal folding trajectory for the atoms of a Coarse-Grained (CG) protein model. The solution of this CG optimization provides an harmonic approximation of the true potential energy surface around the native state. In the next step CG optimization guides the MD simulation by specifying the optimal target positions for the atoms. In turn, MD simulation provides an all-atom conformation whose positions match closely the reference target positions determined by CG optimization. This is accomplished by Targeted Molecular Dynamics (TMD) which uses a bias potential or harmonic restraint in addition to the usual MD potential. Folding is a dynamical process and as such residues make different contacts during the course of folding. Therefore CG optimization has to be reinitialized and repeated over time to accomodate these important changes. At each sampled folding time, the active contacts among the residues are recalculated based on the all-atom conformation obtained from MD. Using the new set of contacts, the CG potential is updated and the CG optimal trajectory for the atoms is recomputed. This is followed by MD. Implementation of this repetitive CG optimization - MD simulation cycle generates the folding trajectory. Simulations on a model protein Villin demonstrate the utility of the method. Since the method is founded on the general tools of optimal control theory and MD without any restrictions, it is widely applicable to other systems. It can be easily implemented with available MD software packages

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities

Polarizable Water Model for the Coarse-Grained MARTINI Force Field

Coarse-grained (CG) simulations have become an essential tool to study a large variety of biomolecular processes, exploring temporal and spatial scales inaccessible to traditional models of atomistic resolution. One of the major simplifications of CG models is the representation of the solvent, which is either implicit or modeled explicitly as a van der Waals particle. The effect of polarization, and thus a proper screening of interactions depending on the local environment, is absent. Given the important role of water as a ubiquitous solvent in biological systems, its treatment is crucial to the properties derived from simulation studies. Here, we parameterize a polarizable coarse-grained water model to be used in combination with the CG MARTINI force field. Using a three-bead model to represent four water molecules, we show that the orientational polarizability of real water can be effectively accounted for. This has the consequence that the dielectric screening of bulk water is reproduced. At the same time, we parameterized our new water model such that bulk water density and oil/water partitioning data remain at the same level of accuracy as for the standard MARTINI force field. We apply the new model to two cases for which current CG force fields are inadequate. First, we address the transport of ions across a lipid membrane. The computed potential of mean force shows that the ions now naturally feel the change in dielectric medium when moving from the high dielectric aqueous phase toward the low dielectric membrane interior. In the second application we consider the electroporation process of both an oil slab and a lipid bilayer. The electrostatic field drives the formation of water filled pores in both cases, following a similar mechanism as seen with atomistically detailed models