LowModeMD--implicit low-mode velocity filtering applied to conformational search of macrocycles and protein loops

J Chem Inf Model. 2010 May 24;50(5):792-800. doi: 10.1021/ci900508k.


We present a method for conformational search of complex molecular systems such as macrocycles and protein loops. The method is based on perturbing an existing conformation along a molecular dynamics trajectory using initial atomic velocities with kinetic energy concentrated on the low-frequency vibrational modes, followed by energy minimization. A novel Chebyshev polynomial filter is used to heavily dampen the high-frequency components of a randomly generated Maxwell-Boltzmann velocity vector. The method is very efficient, even for large systems; it is straightforward to implement and requires only standard force-field energy and gradient evaluations. The results of several computational experiments suggest that the method is capable of efficiently sampling low-strain energy conformations of complex systems with nontrivial nonbonded interaction networks.

MeSH terms

  • Animals
  • Cattle
  • Macrocyclic Compounds / chemistry*
  • Molecular Conformation
  • Molecular Dynamics Simulation* / economics
  • Protein Conformation
  • Proteins / chemistry*
  • rho-Associated Kinases / chemistry


  • Macrocyclic Compounds
  • Proteins
  • rho-Associated Kinases