Tertiary structure prediction of mixed α/β proteins via energy minimization

We describe an improved algorithm for protein structure prediction, assuming that the location of secondary structural elements is known, with particular focus on prediction for proteins containing β‐strands. Hydrogen bonding terms are incorporated into the potential function, supplementing our previously developed residue‐residue potential which is based on a combination of database statistics and an excluded volume term. Two small mixed α/β proteins, 1‐CTF and BPTI, are studied. In order to obtain native‐like structures, it is necessary to allow the β‐strands in BPTI to distort substantially from an ideal geometry, and an automated algorithm to carry this out efficiently is presented. Simulated annealing Monte Carlo methods, which contain a genetic algorithm component as well, are used to produce an ensemble of low‐energy structures. For both proteins, a cluster of structures with low RMS deviation from the native structure is generated and the energetic ranking of this cluster is in the top 2 or 3 clusters obtained from simulations. These results are encouraging with regard to the possibility of constructing a robust procedure for tertiary folding which is applicable to β‐strand containing proteins. Proteins 33:240–252, 1998. © 1998 Wiley‐Liss, Inc.