Mutational Basin-Hopping: Combined Structure and Sequence Optimization for Biomolecules.

Abstract

The study of energy landscapes has led to a good understanding of how and why proteins and nucleic acids adopt their native structure. Through evolution, sequences have adapted until they exhibit a strongly funnelled energy landscape, stabilising the native fold. Design of artificial biomolecules faces the challenge of creating similar stable, minimally frustrated and functional sequences. Here we present a biminimisation approach, mutational basin-hopping, in which we simultaneously use global optimisation to optimise the energy and a target function describing a desired property of the system. This optimisation of structure and sequence is a generalised basin-hopping method, and produces an efficient design process, which can target properties such as binding affinity or solubility.