A Solvent Model for Simulations of Peptides in Bilayers. I. Membrane-Promoting α-Helix Formation

Abstract

We describe an efficient solvation model for proteins. In this model atomic solvation parameters imitating the hydrocarbon core of a membrane, water, and weak polar solvent (octanol) were developed. An optimal number of solvation parameters was chosen based on analysis of atomic hydrophobicities and fitting experimental free energies of gas-cyclohexane, gas-water, and octanol-water transfer for amino acids. The solvation energy term incorporated into the ECEPP/2 potential energy function was tested in Monte Carlo simulations of a number of small peptides with known energies of bilayer-water and octanol-water transfer. The calculated properties were shown to agree reasonably well with the experimental data. Furthermore, the solvation model was used to assess membrane-promoting alpha-helix formation. To accomplish this, all-atom models of 20-residue homopolypeptides-poly-Leu, poly-Val, poly-Ile, and poly-Gly in initial random coil conformation-were subjected to nonrestrained Monte Carlo conformational search in vacuo and with the solvation terms mimicking the water and hydrophobic parts of the bilayer. All the peptides demonstrated their largest helix-forming tendencies in a nonpolar environment, where the lowest-energy conformers of poly-Leu, Val, Ile revealed 100, 95, and 80% of alpha-helical content, respectively. Energetic and conformational properties of Gly in all environments were shown to be different from those observed for residues with hydrophobic side chains. Applications of the solvation model to simulations of peptides and proteins in the presence of membrane, along with limitations of the approach, are discussed.

Dipole lattice membrane model for protein calculations

“…Specifically, the model used by Efremov et al treated the membrane as a homogeneous hydrocarbon. 14,15 Finally, our calculation of the entropy lost due to dipole orientation is quite different from any found in the literature. This sort of term is not relevant in the context of continuum electrostatics; it is only when dielectric response is discretized into a finite number of dipoles that one can reasonably speak of the solvent entropy.…”

Antiamoebin I in Methanol Solution: Rapid Exchange between Right‐Handed and Left‐Handed 310‐Helical Conformations

“…To obtain structural models of these exchanging species, several restrained Monte Carlo simulations were performed using the FANTOM program [55] with the ECEPP/3 force field [56]. For treatment of the solvation effects, the implicit solvation model with the atomic solvation parameters for octanol [57] was used. To narrow the conformational space available for the peptide, restraints to the experimentally observed H-bond pattern were imposed.…”

“…Molecular modeling and Monte Carlo simulations were carried out using the FANTOM program [55] with the ECEPP/3 force field [56]. In the Monte Carlo simulation, an implicit solvation model with atomic solvation parameters derived for gaswater, gas -octanol, and gas -cyclohexane transfer [57] was used. A distance-dependent dielectric permeability e ¼ r was employed, where r is a distance.…”

Implicit two-phase solvation model as a tool to assess conformation and energetics of proteins in membrane-mimetic media

“…ASP sets imitating both the nonpolar hydrocarbon core of the membrane and aqueous solution were taken from Refs. [5,11]. The membrane is described as a two-phase system: water/hydrophobic layer/water ( Fig.…”

“…Recently, we proposed a protein solvation model mimicking polar (water), moderately polar (octanol), and membrane environments [5,11,12]. A full-atom protein representation was used, and the conformational space was sampled in unrestrained MC simulations.…”