Concerted motions in allosteric model proteins at terahertz frequencies

Abstract

PDZ3 is an allosteric protein that represents an ideal test system to analyze the molecular determinants at the basis of the allosteric mechanism. Recent computational studies of the terahertz (THz) fluctuations of this protein have highlighted a response nucleus for binding modulated by the ligand that is visible only at THz frequencies and that overlaps with the known allosterically responding residues (Conti Nibali et al. 2017). With the aim of further characterizing the changes in the terahertz dynamics of this allosteric protein following the binding event, we have carried out an analysis of the correlation motions of pairs of PDZ3 residues from molecular dynamic simulations. We identify concerted and non-random THz fluctuations in the main secondary structure elements of the PDZ3. Importantly, we highlight a concerted motion of some residues belonging to the allosteric response nucleus for binding.