Core-packing constraints, hydrophobicity and protein design

Abstract

Recent crystallographic studies have shown that both backbone and side-chain adjustments occur when different core-packing arrangements are accommodated in proteins. Thus, modeling methods, which have typically considered only side-chain adjustments, must now also account for backbone movements to accurately predict the energies and structures of mutated or designed proteins. The 'plasticity' of protein cores demonstrated by random mutagenesis simplifies protein design by increasing the likelihood of identifying alternative core sequences.