Design of elastic networks with evolutionary optimized long-range communication as mechanical models of allosteric proteins

Abstract

Allosteric effects often underlie the activity of proteins, and elucidating generic design aspects and functional principles unique to allosteric phenomena represent a major challenge. Here an approach consisting of the in silico design of synthetic structures, which, as the principal element of allostery, encode dynamical long-range coupling among two sites, is presented. The structures are represented by elastic networks, similar to coarse-grained models of real proteins. A strategy of evolutionary optimization was implemented to iteratively improve allosteric coupling. In the designed structures, allosteric interactions were analyzed in terms of strain propagation, and simple pathways that emerged during evolution were identified as signatures through which long-range communication was established. Moreover, robustness of allosteric performance with respect to mutations was demonstrated. As it turned out, the designed prototype structures reveal dynamical properties resembling those found in real allosteric proteins. Hence, they may serve as toy models of complex allosteric systems, such as proteins. Application of the developed modeling scheme to the allosteric transition in the myosin V molecular motor was also demonstrated.