Investigating evolutionary lines of least resistance using the inverse protein-folding problem.

Abstract

We present a polynomial time algorithm for estimating optimal HP sequences that fold to a specified target protein conformation based on Sun et al's Grand Canonical (GC) model. Application of the algorithm to related proteins taken from the PDB allows us to explore the nature of the protein genotype:phenotype map. Results suggest: (1) that the GC model captures important biological aspects of the mapping between protein sequences and their corresponding structures, and (2) the set of sequences that map to a target structure with optimal energy is affected by minor differences in structure.