Shape-dependent designability studies of lattice proteins

Abstract

One important problem in computational structural biology is protein designability, that is,why protein sequences are not random strings of amino acids but instead showregular patterns that encode protein structures. Many previous studies that haveattempted to solve the problem have relied upon reduced models of proteins. Inparticular, the 2D square and the 3D cubic lattices together with reduced amino acidalphabet models have been examined extensively and have led to interesting resultsthat shed some light on the evolutionary relationship among proteins. Here weperform designability studies on the 2D square lattice and explore the effects ofvariable overall shapes on protein designability using a binary hydrophobic–polar(HP) amino acid alphabet. Because we rely on a simple energy function thatcounts the total number of H–H interactions between non-sequential residues, werestrict our studies to protein shapes that have the same number of residues andalso a constant number of non-bonded contacts. We have found that there is amarked difference in the designability between various protein shapes, with some ofthem accounting for a significantly larger share of the total foldable sequences.