ATOMIC SOLVATION PARAMETERS FOR PROTEINS IN A MEMBRANE ENVIRONMENT - APPLICATION TO TRANSMEMBRANE ALPHA-HELICES

Several sets of atomic solvation parameters imitating: (i) nonpolar en vironment of hydrocarbon core of a membrane, (ii) aqueous solution, an d (iii) weakly-polar solvents have been developed. The parameters have been incorporated into the ECEPP/2 and CHARMM force fields and employ ed in non-restrained Monte Carlo and molecular dynamics simulations of membrane-spanning or-helical peptides (segment A of bacteriorhodopsin , melittin). Through these simulations, the structure and energetics o f the helices have been examined as a function of the solvation term i n the potential energy function. For the peptides under study, the set (i) of atomic solvation parameters reveals good retention of the alph a-helical conformation. By contrast, the simulations in vacuum or with the parameters imitating a polar solvent (sets (ii) or (iii)) show fa st helix destabilization and tight packing of the structure accompanie d by significant decreasing of the surface area accessible to solvent. Increased helical propensity for amino acid residues, population of s ide-chain rotamers as well as hydrogen-bonding pattern in nonpolar mem brane-like environment agree well with available experimental and comp utational data. The problems related to further applications of the me mbrane-mimicking sets of atomic solvation parameters to simulations of membrane proteins and peptides are addressed.