A virtual-system coupled multicanonical molecular dynamics simulation: Principles and applications to free-energy landscape of protein-protein interaction with an all-atom model in explicit solvent
Abstract
We propose a novel generalized ensemble method, a virtual-system coupled multicanonical molecular dynamics (V-McMD), to enhance conformational sampling of biomolecules expressed by an all-atom model in an explicit solvent. In this method, a virtual system, of which physical quantities can be set arbitrarily, is coupled with the biomolecular system, which is the target to be studied. This method was applied to a system of an Endothelin-1 derivative, KR-CSH-ET1, known to form an antisymmetric homodimer at room temperature. V-McMD was performed starting from a configuration in which two KR-CSH-ET1 molecules were mutually distant in an explicit solvent. The lowest free-energy state (the most thermally stable state) at room temperature coincides with the experimentally determined native complex structure. This state was separated to other non-native minor clusters by a free-energy barrier, although the barrier disappeared with elevated temperature. V-McMD produced a canonical ensemble faster than a conventional McMD method.
- Publication:
-
Journal of Chemical Physics
- Pub Date:
- May 2013
- DOI:
- 10.1063/1.4803468
- Bibcode:
- 2013JChPh.138r4106H
- Keywords:
-
- biological techniques;
- biology computing;
- free energy;
- molecular biophysics;
- molecular dynamics method;
- molecule-molecule reactions;
- proteins;
- 87.15.ap;
- 87.15.B-;
- 87.15.km;
- 87.80.-y;
- Molecular dynamics simulation;
- Structure of biomolecules;
- Protein-protein interactions;
- Biological techniques and instrumentation;
- biomedical engineering