THE USE OF POSITION-SPECIFIC ROTAMERS IN MODEL-BUILDING BY HOMOLOGY

In this study we concentrate on replacing side chains as a subtask of model building by homology. Two problems arise. How to determine poten tial low energy rotamers? And how to avoid the combinatorial explosion that results from the combination of many residues for which multiple good rotamers are predicted? We attempt to solve these problems by ch oosing position-specific rather than generalized rotamers and by sorti ng the residues that have to be modelled as a function of their freedo m in rotamer space. The practical advantages of our method are the qua lity of the models for cases of high backbone similarity, the small am ount of human intervention needed, and the fact that the method automa tically estimates the reliability with which each residue has been mod eled. Other methods described in this issue are probably more suitable if large backbone rearrangements or loop insertions and deletions nee d to be modeled. (C) 1995 Wiley-Liss, Inc.