Discovering free energy basins for macromolecular systems via guided multiscale simulation

Yuriy V. Sereda, Abhishek Singharoy, Martin F. Jarrold, Peter J. Ortoleva

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

An approach for the automated discovery of low free energy states of macromolecular systems is presented. The method does not involve delineating the entire free energy landscape but proceeds in a sequential free energy minimizing state discovery; i.e., it first discovers one low free energy state and then automatically seeks a distinct neighboring one. These states and the associated ensembles of atomistic configurations are characterized by coarse-grained variables capturing the large-scale structure of the system. A key facet of our approach is the identification of such coarse-grained variables. Evolution of these variables is governed by Langevin dynamics driven by thermal-average forces and mediated by diffusivities, both of which are constructed by an ensemble of short molecular dynamics runs. In the present approach, the thermal-average forces are modified to account for the entropy changes following from our knowledge of the free energy basins already discovered. Such forces guide the system away from the known free energy minima, over free energy barriers, and to a new one. The theory is demonstrated for lactoferrin, known to have multiple energy-minimizing structures. The approach is validated using experimental structures and traditional molecular dynamics. The method can be generalized to enable the interpretation of nanocharacterization data (e.g., ion mobility-mass spectrometry, atomic force microscopy, chemical labeling, and nanopore measurements).

Original languageEnglish (US)
Pages (from-to)8534-8544
Number of pages11
JournalJournal of Physical Chemistry B
Volume116
Issue number29
DOIs
StatePublished - Jul 26 2012
Externally publishedYes

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Molecular Dynamics Simulation
Free energy
Hot Temperature
free energy
Nanopores
Lactoferrin
Atomic Force Microscopy
Entropy
Mass Spectrometry
Electron energy levels
simulation
Ions
Molecular dynamics
molecular dynamics
Energy barriers
Labeling
marking
diffusivity
Mass spectrometry
flat surfaces

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Discovering free energy basins for macromolecular systems via guided multiscale simulation. / Sereda, Yuriy V.; Singharoy, Abhishek; Jarrold, Martin F.; Ortoleva, Peter J.

In: Journal of Physical Chemistry B, Vol. 116, No. 29, 26.07.2012, p. 8534-8544.

Research output: Contribution to journalArticle

Sereda, Yuriy V. ; Singharoy, Abhishek ; Jarrold, Martin F. ; Ortoleva, Peter J. / Discovering free energy basins for macromolecular systems via guided multiscale simulation. In: Journal of Physical Chemistry B. 2012 ; Vol. 116, No. 29. pp. 8534-8544.
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