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Int. J. Mol. Sci. 2013, 14(8), 16058-16075; doi:10.3390/ijms140816058

Transition Pathway and Its Free-Energy Profile: A Protocol for Protein Folding Simulations

1 Korea Research Institute of Standards and Science, Daejon 305-340, Korea 2 School of Liberal Arts and Sciences, Korea National University of Transportation, Chungju 380-702, Korea 3 Center for In Silico Protein Science, School of Computational Sciences, Korea Institute for Advanced Study, Seoul 130-722, Korea
* Author to whom correspondence should be addressed.
Received: 15 April 2013 / Revised: 22 July 2013 / Accepted: 29 July 2013 / Published: 2 August 2013
(This article belongs to the collection Protein Folding)
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We propose a protocol that provides a systematic definition of reaction coordinate and related free-energy profile as the function of temperature for the protein-folding simulation. First, using action-derived molecular dynamics (ADMD), we investigate the dynamic folding pathway model of a protein between a fixed extended conformation and a compact conformation. We choose the pathway model to be the reaction coordinate, and the folding and unfolding processes are characterized by the ADMD step index, in contrast to the common a priori reaction coordinate as used in conventional studies. Second, we calculate free-energy profile as the function of temperature, by employing the replica-exchange molecular dynamics (REMD) method. The current method provides efficient exploration of conformational space and proper characterization of protein folding/unfolding dynamics from/to an arbitrary extended conformation. We demonstrate that combination of the two simulation methods, ADMD and REMD, provides understanding on molecular conformational changes in proteins. The protocol is tested on a small protein, penta-peptide of met-enkephalin. For the neuropeptide met-enkephalin system, folded, extended, and intermediate sates are well-defined through the free-energy profile over the reaction coordinate. Results are consistent with those in the literature.
Keywords: molecular dynamics; free energy; reaction coordinate molecular dynamics; free energy; reaction coordinate
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Lee, I.-H.; Kim, S.-Y.; Lee, J. Transition Pathway and Its Free-Energy Profile: A Protocol for Protein Folding Simulations. Int. J. Mol. Sci. 2013, 14, 16058-16075.

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