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

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

Received: 15 April 2013; in revised form: 22 July 2013 / Accepted: 29 July 2013 / Published: 2 August 2013
(This article belongs to the Special Issue Protein Folding 2013)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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
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MDPI and ACS Style

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.

AMA Style

Lee I-H, Kim S-Y, Lee J. Transition Pathway and Its Free-Energy Profile: A Protocol for Protein Folding Simulations. International Journal of Molecular Sciences. 2013; 14(8):16058-16075.

Chicago/Turabian Style

Lee, In-Ho; Kim, Seung-Yeon; Lee, Jooyoung. 2013. "Transition Pathway and Its Free-Energy Profile: A Protocol for Protein Folding Simulations." Int. J. Mol. Sci. 14, no. 8: 16058-16075.

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