When is a potential accurate enough for structure prediction? Theory and application to a random heteropolymer model of protein folding

Abstract

Attempts to predict molecular structure often try to minimize some potential function over a set of structures. Much effort has gone into creating potential functions and into creating algorithms for minimizing these potential functions. This paper develops a formalism that addresses a complementary question: What are the accuracy requirements for a potential function that predicts molecular structure? The formalism is applied to a simple model of a protein structure potential. The results of this calculation suggest that high accuracy predictions (∼1 Å rms deviation in α-carbon positions) of protein structures require monomer–monomer interaction energies accurate to within 5% to 15%. The paper closes with a discussion of the implications of these results for practical structure prediction.