A fresh look at the vibrational and thermodynamic properties of liquids within the soft potential model.

Contrary to the case of solids and gases, where Debye theory and kinetic theory offer a good description for most of the physical properties, a complete theoretical understanding of the vibrational and thermodynamic properties of liquids is still missing. Liquids exhibit a vibrational density of states (VDOS) which does not obey Debye law, and a heat capacity which decreases monotonically with temperature, rather than growing as in solids. Despite many attempts, a simple, complete and widely accepted theoretical framework able to formally derive the aforementioned properties has not been found yet.

Membrane Phase Transitions in Lipid-Wrapped Nanoparticles.

A Landau theory is constructed for the gel/fluid transition of a lipid bilayer wrapped around a spherical nanoparticle (lipid-wrapped nanoparticle, LNP). The bilayer is regarded as a regular solution of gel and fluid lipids with distinct inter- and intralayer interactions plus the interaction of the core with the inner layer. It is required that both the inner and the outer surfaces of the bilayer are perfectly covered with lipids, with the gel and fluid lipids having different areas/lipid.

Moltemplate: A Tool for Coarse-Grained Modeling of Complex Biological Matter and Soft Condensed Matter Physics.

Coarse-grained models have long been considered indispensable tools in the investigation of biomolecular dynamics and assembly. However, the process of simulating such models is arduous because unconventional force fields and particle attributes are often needed, and some systems are not in thermal equilibrium. Although modern molecular dynamics programs are highly adaptable, software designed for preparing all-atom simulations typically makes restrictive assumptions about the nature of the particles and the forces acting on them.

Simulation of fluid/gel phase equilibrium in lipid vesicles.

Simulation of single component dipalmitoylphosphatidylcholine (DPPC) coarse-grained DRY-MARTINI lipid vesicles of diameter 10 nm (1350 lipids), 20 nm (5100 lipids) and 40 nm (17 600 lipids) is performed using statistical temperature molecular dynamics (STMD), to study finite size effects upon the order-disorder gel/fluid transition. STMD obtains enhanced sampling using a generalized ensemble, obtaining a flat energy distribution between upper and lower cutoffs, with little computational cost over canonical molecular dynamics. A single STMD trajectory of moderate length is sufficient to sample 20+ transition events, without trapping in the gel phase, and obtain well averaged properties.

Membrane-wrapped nanoparticles probe divergent roles of GM3 and phosphatidylserine in lipid-mediated viral entry pathways.

Gold nanoparticles (NPs) wrapped in a membrane can be utilized as artificial virus nanoparticles (AVNs) that combine the large nonblinking or bleaching optical cross-section of the NP core with the biological surface properties and functionalities provided by a self-assembled lipid membrane. We used these hybrid nanomaterials to test the roles of monosialodihexosylganglioside (GM3) and phosphatidylserine (PS) for a lipid-mediated targeting of virus-containing compartments (VCCs) in macrophages. GM3-presenting AVNs bind to CD169 (Siglec-1)-expressing macrophages, but inclusion of PS in the GM3-containing AVN membrane decreases binding.

Lipid Packing in Lipid-Wrapped Nanoparticles.

Equilibrium simulations of lipid-wrapped nanoparticles (LNP) were performed using a hybrid molecular dynamics/Monte Carlo (MD/MC) approach. The radius, R, of a spherical nanoparticle (NP) core was adjusted with MC moves while a surrounding lipid bilayer was treated with MD. A wide range of LNP sizes, with the largest R ∼ 40 nm, were studied to determine the average NP radius for a given total number of lipids, N, the number of lipids in each layer, and configurational information.

Membrane Fluidity Sensing on the Single Virus Particle Level with Plasmonic Nanoparticle Transducers.

Viral membranes are nanomaterials whose fluidity depends on their composition, in particular, the cholesterol (chol) content. As differences in the membrane composition of individual virus particles can lead to different intracellular fates, biophysical tools capable of sensing the membrane fluidity on the single-virus level are required. In this manuscript, we demonstrate that fluctuations in the polarization of light scattered off gold or silver nanoparticle (NP)-labeled virus-like-particles (VLPs) encode information about the membrane fluidity of individual VLPs.

Enhanced Sampling of Phase Transitions in Coarse-Grained Lipid Bilayers.

Freezing and melting of dipalmitoylphosphatidylcholine (DPPC) bilayers are simulated in both the explicit (Wet) and implicit solvent (Dry) coarse-grained MARTINI force fields with enhanced sampling, via the isobaric, molecular dynamics version of the generalized replica exchange method (gREM). Phase transitions are described with the entropic viewpoint, based upon the statistical temperature as a function of enthalpy, T(H) = 1/(dS(H)/dH), where S is the configurational entropy. Bilayer thickness, area per lipid, and the second-rank order parameter (P2) are calculated vs temperature in the transition range.

Water Freezing and Ice Melting.

The generalized replica exchange method (gREM) is designed to sample states with coexisting phases and thereby to describe strong first order phase transitions. The isobaric MD version of the gREM is presented and applied to the freezing of liquid water and the melting of hexagonal and cubic ice. It is confirmed that coexisting states are well-sampled.

Pathways through Equilibrated States with Coexisting Phases for Gas Hydrate Formation.

Under ambient conditions, water freezes to either hexagonal ice or a hexagonal/cubic composite ice. The presence of hydrophobic guest molecules introduces a competing pathway: gas hydrate formation, with the guests in clathrate cages. Here, the pathways of the phase transitions are sought as sequences of states with coexisting phases, using a generalized replica exchange algorithm designed to sample them in equilibrium, avoiding nonequilibrium processes.

Isobaric Molecular Dynamics Version of the Generalized Replica Exchange Method (gREM): Liquid-Vapor Equilibrium.

A prescription for sampling isobaric generalized ensembles with molecular dynamics is presented and applied to the generalized replica exchange method (gREM), which was designed to simulate first-order phase transitions. The properties of the isobaric gREM ensemble are discussed, and a study is presented for the liquid-vapor equilibrium of the guest molecules given for gas hydrate formation with the mW water model. Phase diagrams, critical parameters, and a law of corresponding states are obtained.

Entropic Description of Gas Hydrate Ice-Liquid Equilibrium via Enhanced Sampling of Coexisting Phases.

Metastable β ice holds small guest molecules in stable gas hydrates, so its solid-liquid equilibrium is of interest. However, aqueous crystal-liquid transitions are very difficult to simulate. A new molecular dynamics algorithm generates trajectories in a generalized NPT ensemble and equilibrates states of coexisting phases with a selectable enthalpy.

Classical Description of the Vibrational Spectroscopy, Structure, and Electrostatics of the Halide Solvation Shell with the POLIR Potential.

POLIR (POLarizable for IR) (J. Chem. Phys.

The relation between the structure of the first solvation shell and the IR spectra of aqueous solutions.

The spectroscopic signatures of solvated anions and cations, in the O-H stretch region of water, are studied using the POLIR potential. Shifts in the spectra are shown to correlate very well with the distribution of a particular hydrogen bond angle for the waters in the first solvation shell. The results indicate that the spectral shifts might be predicted from MD simulations in a computationally convenient fashion, avoiding an explicit calculation of the spectra, as first suggested by Sharp et al.

Replica exchange statistical temperature molecular dynamics algorithm.

The replica exchange statistical temperature molecular dynamics (RESTMD) algorithm is presented, designed to alleviate an extensive increase of the number of replicas required as system size increases in the conventional temperature replica exchange method (tREM), and to obtain improved sampling in individual replicas. RESTMD optimally integrates multiple STMD (Phys. Rev.

Classical simulations with the POLIR potential describe the vibrational spectroscopy and energetics of hydration: divalent cations, from solvation to coordination complex.

POLIR, a polarizable water potential optimized for vibrational and intermolecular spectroscopy in pure water but not optimized for solvation, is used to describe solutions of the divalent metal cations Ca(2+), Mg(2+), and Cu(2+). The spectral shifts in the O-H stretch region obtained from classical simulations are in agreement with experiment. The water-ion binding energies are dominated by classical electrostatics, even though the Cu(2+) case might be considered to involve an intermediate-strength chemical bond.

Extending classical molecular theory with polarization.

A classical, polarizable, electrostatic theory of short-ranged atom-atom interactions, incorporating the smeared nature of atomic partial charges, is presented. Detailed models are constructed for CO monomer and for CO interacting with an iron atom, as a first step toward heme proteins. A good representation is obtained of the bond-length-dependent dipole of CO monomer from fitting at the equilibrium distance only.

Protein folding and confinement: inherent structure analysis of chaperonin action.

A coarse-grained model of the action of a chaperonin cage of tunable hydrophobicity, h, upon a protein with the possibility of misfolding is studied with inherent structure (IS) analysis and statistical temperature molecular dynamics (STMD) simulation. Near the folding temperature, the equilibrium properties of the system may be understood in terms of <10 IS. The known phenomenon of an optimal cage hydrophobicity for productive folding, found at h = 0.

Classical molecular electrostatics: recognition of ligands in proteins and the vibrational Stark effect.

It is shown that classical electrostatics quantitatively describes both the binding of the diatomic ligands XO (X = C, N, O) to the heme group in myoglobin and the dependence of their vibrational frequencies upon an external field, the vibrational Stark effect. The key is a proper treatment of induced dipoles. The results suggest that ligand binding occurs via an "electrostatic bond", a generalization of the standard ionic bond to include induction, and, more generally, that classical electrostatics can replace quantum mechanics for a considerable simplification of some complex problems.