Stiff Spring Approximation Revisited: Inertial Effects in Nonequilibrium Trajectories.

Use of harmonic guiding potentials is the most commonly adopted method for implementing steered molecular dynamics (SMD) simulations, performed to obtain potentials of mean force (PMFs) using Jarzynski's equality and other nonequilibrium work (NEW) theorems. The stiff spring approximation (SSA) of Schulten and co-workers enables calculation of the PMF by using the work performed along many SMD trajectories in NEW theorems. We discuss and demonstrate how a high spring constant, k, required for the validity of the SSA can violate another requirement of SSA, the validity of Brownian dynamics in the system under study.

A Permeability Study of O2 and the Trace Amine p-Tyramine through Model Phosphatidylcholine Bilayers.

We study here the permeability of the hydrophobic O2 molecule through a model DPPC bilayer at 323K and 350K, and of the trace amine p-tyramine through PC bilayers at 310K. The tyramine results are compared to previous experimental work at 298K. Nonequilibrium work methods were used in conjunction to simultaneously obtain both the potential of mean force (PMF) and the position dependent transmembrane diffusion coefficient, D(z), from the simulations.

Implementation of the forward-reverse method for calculating the potential of mean force using a dynamic restraining protocol.

We present a new sampling and analysis scheme for calculating the potential of mean force (PMF) of systems studied by steered molecular dynamics simulations. This scheme, which we call the bin-passing method, is based on the forward-reverse (FR) method (due to I. Kosztin and co-workers, Kosztin et al.

McMillan-Mayer theory of solutions revisited: simplifications and extensions.

McMillan and Mayer (MM) proved two remarkable theorems in their paper on the equilibrium statistical mechanics of liquid solutions. They first showed that the grand canonical partition function for a solution can be reduced to one with an effectively solute-only form, by integrating out the solvent degrees of freedom. The total effective solute potential in the effective solute grand partition function can be decomposed into components which are potentials of mean force for isolated groups of one, two, three, etc.

Dynamic turn conformation of a short tryptophan-rich cationic antimicrobial peptide and its interaction with phospholipid membranes.

Cationic antimicrobial peptides are promising sources for novel therapeutic agents against multi-drug-resistant bacteria. HHC-36 (KRWWKWWRR) is a simple but effective antimicrobial peptide with similar or superior activity compared with several conventional antibiotics. In this biophysical study, unique conformational properties of this peptide and some of its analogs as well as its interaction with lipid membranes are investigated in detail.

Membrane permeability of trace amines: evidence for a regulated, activity-dependent, nonexocytotic, synaptic release.

Both pre- and post-synaptic effects of trace amines have been demonstrated. The putative intracellular location of Trace Amine-Associated Receptors necessitate that membrane transport processes be present in order for post-synaptic effects to occur. Here we examine the ability of trace amines to cross synthetic (Fluorosomes) and native (synaptosomes) lipid bilayer membranes.

Calculating diffusion and permeability coefficients with the oscillating forward-reverse method.

The forward-reverse or FR method is an efficient bidirectional work method for determining the potential of mean force w(z) and also supposedly gives in principle the position-dependent diffusion coefficient D(z). Results from a variation called the OFR (oscillating FR) method suggest inconsistencies in the D(z) values when calculated as prescribed by the FR method. A new steering protocol has thus been developed and applied to the OFR method for the accurate determination of D(z) and also provides greater convergence for w(z) in molecular dynamics simulations.

Scattering density profile model of POPG bilayers as determined by molecular dynamics simulations and small-angle neutron and X-ray scattering experiments.

We combine molecular dynamics (MD) simulations and experiment, both small-angle neutron (SANS) and small-angle X-ray scattering (SAXS), to determine the precise structure of bilayers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), a lipid commonly encountered in bacterial membranes. Experiment and simulation are used to develop a one-dimensional scattering density profile (SDP) model suitable for the analysis of experimental data. The joint refinement of such data (i.

Drift-oscillatory steering with the forward-reverse method for calculating the potential of mean force.

We present a method that enables the use of the forward-reverse (FR) method of Kosztin et al. on a broader range of problems in soft matter physics. Our method, which we call the oscillating forward-reverse (OFR) method, adds an oscillatory steering potential to the constant velocity steering potential of the FR method.

Molecular dynamics-based simulation of trace amine membrane permeability.

Trace amines are endogenous compounds, typified by 2-phenylethylamine (PE) and p-tyramine (TA), found in the vertebrate central nervous system. Although synthesized in pre-synaptic terminals, trace amines do not appear to act as neurotransmitters, but rather modulate responsivity to co-existing neurotransmitters. Trace amines are neither actively accumulated in synaptic vesicles, nor released in an activity-dependent manner.

Binding free energy and counterion release for adsorption of the antimicrobial peptide lactoferricin B on a POPG membrane.

Molecular dynamics (MD) simulations are used to study the interaction of an anionic palmitoyl-oleoyl-phosphatidylglycerol (POPG) bilayer with the cationic antimicrobial peptide bovine lactoferricin (LFCinB) in a 100 mM NaCl solution at 310 K. The interaction of LFCinB with a POPG bilayer is employed as a model system for studying the details of membrane adsorption selectivity of cationic antimicrobial peptides. Seventy eight 4 ns MD production run trajectories of the equilibrated system, with six restrained orientations of LFCinB at 13 different separations from the POPG membrane, are generated to determine the free energy profile for the peptide as a function of the distance between LFCinB and the membrane surface.

Prediction of binding free energy for adsorption of antimicrobial peptide lactoferricin B on a POPC membrane.

Molecular dynamics (MD) simulations are used to study the interaction of a zwitterionic palmitoyl-oleoyl-phosphatidylcholine (POPC) bilayer with the cationic antimicrobial peptide bovine lactoferricin (LFCinB) in a 100 mM NaCl solution at 310 K. The interaction of LFCinB with POPC is used as a model system for studying the details of membrane-peptide interactions, with the peptide selected because of its antimicrobial nature. Seventy-two 3 ns MD simulations, with six orientations of LFCinB at 12 different distances from a POPC membrane, are carried out to determine the potential of mean force (PMF) or free energy profile for the peptide as a function of the distance between LFCinB and the membrane surface.