Elements and modulation of functional dynamics.

The existing structure-function paradigm of drug discovery has been evolving toward the essential incorporation of dynamics data. This new functional dynamics paradigm emphasizes. conformational entropy as a driving force of protein function and intermolecular recognition Conformation dynamics (a proxy of conformational entropy) impacts the degree of protein (dis)order and the constitution of the confromational ensemble, the mechanism of allostery and drug resistance, and the free energy of ligand binding, Specific protein and ligand conformations facilitate favorable, reciprocal interactions. The number of protein and ligand conformers that exhibit favorable binding interaction will vary from system to system. All binding scenarios can modulate protein dynamics by various levels of enthalpic and entropic contribution, with significant influence on the functional dynamics of the system. Analysis and consideration of resulting changes of activity, signaling, catalysis, and subsequent phenotypic outcome are powerful motivations in the drug design process.