When and how the homologs can overcome errors in the energy estimates and make the 3D structure prediction possible

One still cannot predict the 3D fold of a protein from its,amino acid seque nce, mainly because of errors in the energy estimates underlying the predic tion. However, a recently developed theory [1] shows that having a set of h omologs (i.e., the chains with equal, in despite of numerous mutations, 3D folds) one can average the potential of each interaction over the homologs and thus predict the common 3 fold of protein family even when a correct fo ld prediction for an individual sequence is impossible because the energies are known only approximately. This theoretical conclusion has been verifie d by simulation of the energy spectra of simplified models of protein chain s [2], and the further investigation of these simplified models shows that their true <<native>> fold can be found by folding of the chain where each interaction potential is averaged over the homologs. In conclusion, the app licability of the <<homolog-averaging>> approach is tested by recognition o f real protein 3D structures. Both the gapless threading of sequences onto the known protein folds [3] and the more practically important gapped threa ding (which allows to consider not only the known 3D structures, but the mo re or less similar to them folds as well) shows a significant increase in s electivity of the native chain fold recognition.