Abstract
A protein-folding algorithm, based on short-range and geometrical long-range restrictions, is applied to bovine pancreatic trypsin inhibitor (BPTI). These restrictions are used to define a starting conformation, SI, by means of a space-filling model of the protein, whose energy is then minimized. The long-range restriction is the imposition of the native spatial geometric arrangement of the loops (SGAL) formed by the disulfide bonds. The short-range restrictions are applied as follows: the (varphi, psi) map of each residue is divided into six regions (corresponding to the right- and left-handed alpha-helical, extended, right- and left-handed bridge, and coil states) and the individual residues are placed in the states of the native structure [although not in conformations with the correct values of (varphi, psi)]. Minimization of the energy of SI leads to a structure, SF, with a root-mean-square deviation of 4.4 A from NI, a previously energy-optimized version of the x-ray structure. SF is closer to the native structure than is the structure RF, which was obtained previously by imposing only the correct SGAL as a restriction. The energy of SF is much lower than that of RF but still larger than the energy of NF (the energy-refined x-ray structure).