Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains. Academic Article uri icon

Overview

abstract

  • With the aim of investigating the relationship between the fast fluctuations of proteins and their allosteric behavior, we perform molecular dynamics simulations of two model PDZ domains with differential allosteric responses. We focus on protein dynamics in the THz regime (0.1-3 THz) as opposed to lower frequencies. By characterizing the dynamic modulation of the protein backbone induced by ligand binding in terms of single residue and pairwise distance fluctuations, we identify a response nucleus modulated by the ligand that is visible only at THz frequencies. The residues of this nucleus undergo a significant stiffening and an increase in mutual coordination upon binding. Additionally, we find that the dynamic modulation is significantly more intense for the side chains, where it is also redistributed to distal regions not immediately in contact with the ligand allowing us to better define the response nucleus at THz frequencies. The overlap between the known allosterically responding residues of the investigated PDZ domains and the modulated region highlighted here suggests that fast THz dynamics could play a role in allosteric mechanisms.

publication date

  • October 31, 2017

Research

keywords

  • Molecular Dynamics Simulation
  • PDZ Domains
  • Proteins
  • Terahertz Spectroscopy

Identity

PubMed Central ID

  • PMC6421520

Scopus Document Identifier

  • 85033605126

Digital Object Identifier (DOI)

  • 10.1016/S1097-2765(04)00086-3

PubMed ID

  • 28991478

Additional Document Info

volume

  • 121

issue

  • 44