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Keywords:

  • Boltzmann sampling;
  • computational chemistry;
  • conformational analysis;
  • molecular dynamics simulations;
  • protein structure

Abstract

A method for conformational Boltzmann sampling of loops in proteins in aqueous solution is presented that is based on adiabatic decoupling molecular dynamics (MD) simulation with temperature or force scaling. To illustrate the enhanced sampling, the loop from residues 33 to 43 in the bovine protein ribonuclease A is adiabatically decoupled from the rest of the protein and the solvent with a mass scaling factor sm=1000 and the sampling is enhanced with a scaling of the temperature using sT=2 or of the force using sV=0.667. Over 5 ns of simulation the secondary structure of the protein remains unaltered while a combined dihedral-angle conformational cluster analysis shows an increase of conformations outside the first most populated cluster of loop conformations for adiabatic decoupling MD with temperature scaling using sT=2 or force scaling using sV=0.667 compared to the standard MD simulation. The atom-positional root-mean-square fluctuations of the Cα atoms of the loop show an increase in the movement of the loop as well, indicating that adiabatic decoupling MD with upscaling of the temperature or downscaling of the force is a promising method for conformational Boltzmann sampling.