Efficient Simulation of Explicitly Solvated Proteins in the Well-Tempered Ensemble

Michael Deighan; Massimiliano Bonomi; Jim Pfaendtner

doi:10.1021/ct300297t

Efficient Simulation of Explicitly Solvated Proteins in the Well-Tempered Ensemble

J Chem Theory Comput. 2012 Jul 10;8(7):2189-92. doi: 10.1021/ct300297t. Epub 2012 Jun 20.

Authors

Michael Deighan¹, Massimiliano Bonomi², Jim Pfaendtner¹

Affiliations

¹ University of Washington Department of Chemical Engineering, Seattle, Washington, United States.
² Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and §California Institute of Quantitative Biosciences, University of California, San Francisco, California, United States.

PMID: 26588950
DOI: 10.1021/ct300297t

Abstract

Herein, we report significant reduction in the cost of combined parallel tempering and metadynamics simulations (PTMetaD). The efficiency boost is achieved using the recently proposed well-tempered ensemble (WTE) algorithm. We studied the convergence of PTMetaD-WTE conformational sampling and free energy reconstruction of an explicitly solvated 20-residue tryptophan-cage protein (trp-cage). A set of PTMetaD-WTE simulations was compared to a corresponding standard PTMetaD simulation. The properties of PTMetaD-WTE and the convergence of the calculations were compared. The roles of the number of replicas, total simulation time, and adjustable WTE parameter γ were studied.