A Solvent Model for Simulations of Peptides in Bilayers. II. Membrane-Spanning α-Helices

AbstractWe describe application of the implicit solvation model (see the first paper of this series), to Monte Carlo simulations of several peptides in bilayer- and water-mimetic environments, and in vacuum. The membrane-bound peptides chosen were transmembrane segments A and B of bacteriorhodopsin, the hydrophobic segment of surfactant lipoprotein, and magainin2. Their conformations in membrane-like media are known from the experiments. Also, molecular dynamics study of surfactant lipoprotein with different explicit solvents has been reported (Kovacs, H., A. E. Mark, J. Johansson, and W. F. van Gunsteren. 1995. J. Mol. Biol. 247:808–822). The principal goal of this work is to compare the results obtained in the framework of our solvation model with available experimental and computational data. The findings could be summarized as follows: 1) structural and energetic properties of studied molecules strongly depend on the solvent; membrane-mimetic media significantly promote formation of α-helices capable of traversing the bilayer, whereas a polar environment destabilizes α-helical conformation via reduction of solvent-exposed surface area and packing; 2) the structures calculated in a membrane-like environment agree with the experimental ones; 3) noticeable differences in conformation of surfactant lipoprotein assessed via Monte Carlo simulation with implicit solvent (this work) and molecular dynamics in explicit solvent were observed; 4) in vacuo simulations do not correctly reproduce protein-membrane interactions, and hence should be avoided in modeling membrane proteins

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

AbstractWe 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 α-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 α-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

PhytAMP: a database dedicated to antimicrobial plant peptides

Plants produce small cysteine-rich antimicrobial peptides as an innate defense against pathogens. Based on amino acid sequence homology, these peptides were classified mostly as α-defensins, thionins, lipid transfer proteins, cyclotides, snakins and hevein-like. Although many antimicrobial plant peptides are now well characterized, much information is still missing or is unavailable to potential users. The compilation of such information in one centralized resource, such as a database would therefore facilitate the study of the potential these peptide structures represent, for example, as alternatives in response to increasing antibiotic resistance or for increasing plant resistance to pathogens by genetic engineering. To achieve this goal, we developed a new database, PhytAMP, which contains valuable information on antimicrobial plant peptides, including taxonomic, microbiological and physicochemical data. Information is very easy to extract from this database and allows rapid prediction of structure/function relationships and target organisms and hence better exploitation of plant peptide biological activities in both the pharmaceutical and agricultural sectors. PhytAMP may be accessed free of charge at http://phytamp.pfba-lab.org

On the use of a spectroscopic force field in molecular dynamics simulations

It has been shown that cross-terms in the empirical molecular force field are required in order to correctly reproduce the experimental vibrational frequencies and hence lend confidence in Molecular Dynamics simulations. The 1-3 non bonded interaction for bond angles (the Urey-Bradley term) is added and the redundancy problem arising from the introduction of this new internal coordinate is solved. As a result, cross-terms between bond stretching and bond angle bending coordinates are rationally introduced that give the «spectroscopic« quality to the force field. Applications to Molecular Dynamics simulations of a biomembrane model are described