A fast conformational search strategy for finding low energy structures of model proteins

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Abstract
We describe a new computer algorithm for finding low‐energy conformations of proteins. It is a chain‐growth method that uses a heuristic bias function to help assemble a hydrophobic core. We call it the Core‐directed chain Growth method (CG). We test the CG method on several well‐known literature examples of HP lattice model proteins [in which proteins are modeled as sequences of hydrophobic (H) and polar (P) monomers], ranging from 20–64 monomers in two dimensions, and up to 88‐mers in three dimensions. Previous nonexhaustive methods—Monte Carlo, a Genetic Algorithm, Hydrophobic Zippers, and Contact Interactions—have been tried on these same model sequences. CG is substantially better at finding the global optima, and avoiding local optima, and it does so in comparable or shorter times. CG finds the global minimum energy of the longest HP lattice model chain for which the global optimum is known, a 3D 88‐mer that has only been reachable before by the CHCC complete search method. CG has the potential advantage that it should have nonexponential scaling with chain length. We believe this is a promising method for conformational searching in protein folding algorithms.