Adaptive lambda square dynamics simulation: an efficient conformational sampling method for biomolecules

J Comput Chem. 2014 Jan 5;35(1):39-50. doi: 10.1002/jcc.23462. Epub 2013 Oct 26.


A novel, efficient sampling method for biomolecules is proposed. The partial multicanonical molecular dynamics (McMD) was recently developed as a method that improved generalized ensemble (GE) methods to focus sampling only on a part of a system (GEPS); however, it was not tested well. We found that partial McMD did not work well for polylysine decapeptide and gave significantly worse sampling efficiency than a conventional GE. Herein, we elucidate the fundamental reason for this and propose a novel GEPS, adaptive lambda square dynamics (ALSD), which can resolve the problem faced when using partial McMD. We demonstrate that ALSD greatly increases the sampling efficiency over a conventional GE. We believe that ALSD is an effective method and is applicable to the conformational sampling of larger and more complicated biomolecule systems.

Keywords: all-atom model; explicit water; free energy landscape; generalized ensemble method; partial system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Conformation
  • Molecular Dynamics Simulation*
  • Oligopeptides / chemistry*
  • Polylysine / chemistry*


  • Oligopeptides
  • Polylysine