6533b7dbfe1ef96bd127163b
RESEARCH PRODUCT
Reconstructing the free-energy landscape of Met-enkephalin using dihedral principal component analysis and well-tempered metadynamics
Patrick SenetFrançois Sicardsubject
Protein ConformationSurface PropertiesEnkephalin MethionineFOS: Physical sciencesGeneral Physics and AstronomyDihedral angle01 natural scienceslaw.invention03 medical and health scienceslaw0103 physical sciencesComputer SimulationCartesian coordinate systemPhysics - Biological PhysicsStatistical physicsPhysical and Theoretical ChemistryProtein secondary structureReference modelComputingMilieux_MISCELLANEOUS030304 developmental biologyMathematicsPrincipal Component AnalysisQuantitative Biology::Biomolecules0303 health sciences010304 chemical physicsMetadynamicsEnergy landscapeBiomolecules (q-bio.BM)Condensed Matter - Other Condensed Matter[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistryQuantitative Biology - BiomoleculesBiological Physics (physics.bio-ph)FOS: Biological sciencesPrincipal component analysis[ CHIM.THEO ] Chemical Sciences/Theoretical and/or physical chemistryPhysics::Accelerator PhysicsThermodynamicsEnergy MetabolismAlgorithmsOther Condensed Matter (cond-mat.other)Ramachandran plotdescription
Well-Tempered Metadynamics (WTmetaD) is an efficient method to enhance the reconstruction of the free-energy surface of proteins. WTmetaD guarantees a faster convergence in the long time limit in comparison with the standard metadynamics. It still suffers however from the same limitation, i.e. the non trivial choice of pertinent collective variables (CVs). To circumvent this problem, we couple WTmetaD with a set of CVs generated from a dihedral Principal Component Analysis (dPCA) on the Ramachadran dihedral angles describing the backbone structure of the protein. The dPCA provides a generic method to extract relevant CVs built from internal coordinates. We illustrate the robustness of this method in the case of the small and very diffusive Metenkephalin pentapeptide, and highlight a criterion to limit the number of CVs necessary to biased the metadynamics simulation. The free-energy landscape (FEL) of Met-enkephalin built on CVs generated from dPCA is found rugged compared with the FEL built on CVs extracted from PCA of the Cartesian coordinates of the atoms.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-06-01 |