Thermodynamics of allostery paves a way to allosteric drugs
We overview here our recent work on the thermodynamic view of allosteric regulation and communication. Starting from the geometry-based prediction of regulatory binding sites in a static structure, we move on to exploring a connection between ligand binding and the intrinsic dynamics of the protein molecule. We describe here two recently introduced measures, binding leverage and leverage coupling, which allow one to analyze the molecular basis of allosteric regulation. We discuss the advantages of these measures and show that they work universally in proteins of different sizes, oligomeric states, and functions. We also point to the problems that have to be solved before completing an atomic level description of allostery, and briefly discuss ideas for computational design of allosteric drugs. âº Recent works on thermodynamic view of allostery are discissed. âº Local closeness is a static, geometry-based predictor of binding sites âº Binding leverage links effect of ligand binding to function-related conformational changes âº Leverage coupling allows to quantify allosteric communication. âº Ideas for design of allosteric drugs are discussed.