Conformational subspace in simulation of early‐stage protein folding

A probability calculus was used to simulate the early stages of protein folding in ab initio structure prediction. The probabilities of particular ϕ and ψ angles for each of 20 amino acids as they occur in crystal forms of proteins were used to calculate the amount of information necessary for the occurrence of given ϕ and ψ angles to be predicted. It was found that the amount of information needed to predict ϕ and ψ angles with 5° precision is much higher than the amount of information actually carried by individual amino acids in the polypeptide chain. To handle this problem, a limited conformational space for the preliminary search for optimal polypeptide structure is proposed based on a simplified geometrical model of the polypeptide chain and on the probability calculus. These two models, geometric and probabilistic, based on different sources, yield a common conclusion concerning how a limited conformational space can represent an early stage of polypeptide chain‐folding simulation. The ribonuclease molecule was used to test the limited conformational space as a tool for modeling early‐stage folding. Proteins 2004. © 2004 Wiley‐Liss, Inc.