Structurally Constrained Protein Evolution: Results From a Lattice Simulation

Abstract

. We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We use a cubic lattice model of the protein structure and test the neutrality conditions by extensive Monte Carlo simulations. We observe that sequence space is traversed by neutral networks, i.e. sets of sequences with the same fold connected by point mutations. Typical pairs of sequences on a neutral network are nearly as di#erent as randomly chosen sequences. The fraction of neutral neighbors has strong sequence to sequence variations, which influence the rate of neutral evolution. In this paper we study the thermodynamic stability of di#erent protein sequences. We relate the high variability of the fraction of neutral mutations to the complex energy landscape within a neutral network, arguing that valleys in this landscape are associated..