Coupling of global and local vibrational modes in dynamic allostery of proteins.

It is now recognized that internal global protein dynamics play an important role in the allosteric function of many proteins. Alterations of protein flexibility on effector binding affect the entropic cost of binding at a distant site. We present a coarse-grained model for a potential amplification of such entropic allostery due to coupling of fast, localized modes to the slow, global modes. We show how such coupling can give rise to large compensating entropic and enthalpic terms. The model corresponds to the pattern of calorimetry and NMR data from experiments on the Met repressor.