Ensemble-Biased Metadynamics: A Molecular Simulation Method to Sample Experimental Distributions. Biophys J 2015 Jun 16;108(12):2779-82
Date
06/18/2015Pubmed ID
26083917Pubmed Central ID
PMC4472218DOI
10.1016/j.bpj.2015.05.024Scopus ID
2-s2.0-84931269561 (requires institutional sign-in at Scopus site) 62 CitationsAbstract
We introduce an enhanced-sampling method for molecular dynamics (MD) simulations referred to as ensemble-biased metadynamics (EBMetaD). The method biases a conventional MD simulation to sample a molecular ensemble that is consistent with one or more probability distributions known a priori, e.g., experimental intramolecular distance distributions obtained by double electron-electron resonance or other spectroscopic techniques. To this end, EBMetaD adds an adaptive biasing potential throughout the simulation that discourages sampling of configurations inconsistent with the target probability distributions. The bias introduced is the minimum necessary to fulfill the target distributions, i.e., EBMetaD satisfies the maximum-entropy principle. Unlike other methods, EBMetaD does not require multiple simulation replicas or the introduction of Lagrange multipliers, and is therefore computationally efficient and straightforward in practice. We demonstrate the performance and accuracy of the method for a model system as well as for spin-labeled T4 lysozyme in explicit water, and show how EBMetaD reproduces three double electron-electron resonance distance distributions concurrently within a few tens of nanoseconds of simulation time. EBMetaD is integrated in the open-source PLUMED plug-in (www.plumed-code.org), and can be therefore readily used with multiple MD engines.
Author List
Marinelli F, Faraldo-Gómez JDAuthor
Fabrizio Marinelli PhD Associate Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Molecular Dynamics SimulationProtein Conformation
Software
