Prediction of residue-residue pair frequencies in proteins

Knowledge of how frequently different types of residues are found near each other in protein structures has been widely used in threading and in simul ating protein folding. In this paper we show that the residue-residue pair frequencies can be reproduced by a simple, physical model. The central comp onent is the nonpolar in-charge out character. This character was captured by obtaining for each type of residue the relative density at a given dista nce from the protein's center of geometry. These densities were convenientl y fitted to exponential or linear functions of the radial distance and used to generate atomic positions. To account for chain connectivity, distances between residue pairs were constrained by independent Gaussian functions, which have increasing means and deviations for increasing sequence separati ons. Interactions between nonpolar residues and between charged residues we re found to extend up to a distance of similar to7.5 Angstrom and the inter action potentials extracted appear to be an intrinsic property. This radial -distance based model, constructed and tested on a set of 243 nonhomologous proteins, has' a clear physical basis and may hold important clues for str ucture prediction.