Localization of Millisecond Dynamics: Dihedral Entropy from Accelerated MD

J Chem Theory Comput. 2016 Aug 9;12(8):3449-55. doi: 10.1021/acs.jctc.6b00231. Epub 2016 Jul 11.

Abstract

Here, we demonstrate a method to capture local dynamics on a time scale 3 orders of magnitude beyond state-of-the-art simulation approaches. We apply accelerated molecular dynamics simulations for conformational sampling and extract reweighted backbone dihedral distributions. Local dynamics are characterized by torsional probabilities, resulting in residue-wise dihedral entropies. Our approach is successfully validated for three different protein systems of increasing size: alanine dipeptide, bovine pancreatic trypsin inhibitor (BPTI), and the major birch pollen allergen Bet v 1a. We demonstrate excellent agreement of flexibility profiles with both large-scale computer simulations and NMR experiments. Thus, our method provides efficient access to local protein dynamics on extended time scales of high biological relevance.

MeSH terms

  • Alanine / chemistry
  • Animals
  • Antigens, Plant / chemistry*
  • Antigens, Plant / metabolism
  • Aprotinin / chemistry*
  • Aprotinin / metabolism
  • Cattle
  • Dipeptides / chemistry*
  • Dipeptides / metabolism
  • Entropy
  • Magnetic Resonance Spectroscopy
  • Molecular Dynamics Simulation*

Substances

  • Antigens, Plant
  • Dipeptides
  • Aprotinin
  • Alanine