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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 Special Issue Protein Folding 2015)
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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) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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