Genetic algorithms for protein tertiary structure prediction

Abstract

This article describes the application of genetic algorithms to the problem of protein tertiary structure prediction. The genetic algorithm is used to search a set of energetically sub-optimal conformations. A hybrid representation of proteins, three operators MUTATE, SELECT and CROSSOVER and a fitness function, that consists of a simple force field were used. The prototype was applied to the ab initio prediction of Crambin. None of the conformations generated by the genetic algorithm are similar to the native conformation, but all show much lower energy than the native structure on the same force field. This means the genetic algorithm's search was successful but the fitness function was not a good indicator for native structure. In another experiment, the backbone was held constant in the native state and only side chains were allowed to move. For Crambin, this produced an alignment of 1.86 Å r.m.s. from the native structure.