ROLE OF ELECTROSTATIC SCREENING IN DETERMINING PROTEIN MAIN-CHAIN CONFORMATIONAL PREFERENCES

Amino acids display significant variation in propensity for the alpha( R)-helical, beta-sheet; and other main chain conformational states in proteins and peptides. The physical reason for these preferences remai ns controversial. Conformational entropy, steric factors, and the hydr ophobic effect have all been advanced as the dominant underlying cause . Iii this work,we explore the role of a fourth factor, electrostatics , in determining the main chain conformation in protein molecules. Pot entials of mean force derived from experimental protein structures ard used to evaluate the free energy of electrostatic and other interacti ons of a residue in a protein environment. The local and nonideal elec trostatic interactions of main chain polar atoms are found to be cruci al for determining the preferences of residues for the alpha(R)-helica l state: and other main chain conformational states of a residue. Furt her, the strength of local and nonlocal electrostatic interactions is shown to depend on the electrostatic screening by:solvent and protein groups. Residue specific modulation of this screening in a manner rela ted to side chain bulk and squatness produces a model that fits the ob served distribution bf residue conformations in proteins and recent ex perimental mutagenesis data on protein stability better than any other single factor.