Model building of disulfide bonds in proteins with known three-dimensional structure.

As an aid in the selection of sites in a protein where a disulfide bond might be engineered, a computer program has been developed. The algorithm starts with the generation of C beta positions from the N, C alpha and C atom coordinates available from a three-dimensional model. A first set of residue pairs that might form a disulfide bond is selected on the basis of C beta-C beta distances between residues. Then, for each residue in this set, S gamma positions are generated, which satisfy the requirement that, with ideal values for the C alpha-C beta and C beta-S gamma bond lengths and for the bond angle at C beta, the distance between S gamma of residue 1 and C beta of residue 2 in a pair (determined by the bond angle at S gamma 2) is at, or very close to its ideal value. Usually two acceptable S gamma positions are found for each half cystine, resulting in up to four different conformations for the disulfide bond. Finally, these conformations are subjected to an energy minimization procedure to remove large deviations from ideal geometry and their final energies are calculated. User input determines which final conformations are energetically acceptable. These conformations are written to a file to allow further analysis and e.g. inspection on a computer graphics device.