DETERMINANTS OF SECONDARY STRUCTURE OF POLYPEPTIDE-CHAINS - INTERPLAYBETWEEN SHORT-RANGE AND BURIAL INTERACTIONS

The effect of tertiary interactions on the observed secondary structur e found in the native conformation of globular proteins was examined i n the context of a reduced protein model. Short-range interactions are controlled by knowledge based statistical potentials that reflect loc al conformational regularities seen in a; database of three-dimensiona l protein structures. Long-range interactions are approximated by mean field, single residue based, centrosymmetric hydrophobic burial poten tials. Even when pairwise specific long-range interactions are ignored , the inclusion of such burial preferences noticeably modifies the equ ilibrium chain conformations, and the observed secondary structure is closer to that seen in the folded state. For a test set of 10 proteins (belonging to various structural classes), the accuracy of secondary structure prediction is about 66% and increases by 9% with respect to a related model based on short-range interactions alone [Kolinski et a l., J. Chem. Phys. 103, 4312 (1995)]. The increased accuracy is due to the interplay between the short-range conformational propensities and the burial and compactness requirements built into the present model. While the absolute level of accuracy assessed on a per residue basis is comparable to more standard techniques, in contrast to these approa ches, the conformation of the chain now has a better defined geometric context. For example, the assumed spherical domain protein model that simulates the segregation of residues between the hydrophobic core an d the hydrophilic surface allows for the prediction of surface loops/t urns where the polypeptide chain changes its direction. The implicatio ns of having such self-consistent secondary structure predictions for the prediction of protein tertiary structure are briefly discussed. (C ) 1997 American Institute of Physics.