Amino acid residue environments and predictions of residue type

The determination of a protein's structure from the knowledge of its linear chain is one of the important problems that remains as a bottleneck in int erpreting the rapidly increasing repository of genetic sequence data. One a pproach to this problem that has shown promise and given a measure of succe ss is threading. In this approach contact energies between different amino acids are first determined by statistical methods applied to known structur es. These contact energies are then applied to a sequence whose structure i s to be determined by threading it through various known structures and det ermining the total threading energy for each candidate structure. That stru cture that yields the lowest total energy is then considered the leading ca ndidate among all the structures tested. Additional information is often ne eded in order to support the results of threading studies, as it is well kn own in the field that the contact potentials used are not sufficiently sens itive to allow definitive conclusions. Here, we investigate the hypothesis that the environment of an amino acid residue realized as all those residue s not local to it on the chain but sufficiently close spatially can supply information predictive of the type of that residue that is not adequately r eflected in the individual contact energies. We present evidence that confi rms this hypothesis and suggests a high order cooperativity between the res idues that surround a given residue and how they interact with it. We sugge st a possible application to threading. (C) 2001 Elsevier Science Ltd. All rights reserved.