United-residue force field for off-lattice protein-structure simulations: III. Origin of backbone hydrogen-bonding cooperativity in united-residue potentials

Abstract

Based on the dipole model of peptide groups developed in our earlier work [Liwo et al., Prot. Sci., 2, 1697 (1993)], a cumulant expansion of the average free energy of the system of freely rotating peptide-group dipoles tethered to a fixed α-carbon trace is derived. A graphical approach is presented to find all nonvanishing terms in the cumulants. In particular, analytical expressions for three- and four-body (correlation) terms in the averaged interaction potential of united peptide groups are derived. These expressions are similar to the cooperative forces in hydrogen bonding introduced by Koliński and Skolnick [J. Chem. Phys., 97, 9412 (1992)]. The cooperativity arises here naturally from the higher order terms in the power-series expansion (in the inverse of the temperature) for the average energy. Test calculations have shown that addition of the derived four-body term to the statistical united-residue potential of our earlier work [Liwo et al., J. Comput. Chem., 18, 849, 874 (1997)] greatly improves its performance in folding poly-l-alanine into an α-helix. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 259–276, 1998