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

International Journal of Molecular Sciences

In-Ho Lee¹  Seung-Yeon Kim² 

[1] Korea Research Institute of Standards and Science, Daejon 305-340, Korea; E-Mail:;School of Liberal Arts and Sciences, Korea National University of Transportation, Chungju 380-702, Korea; E-Mail:

关键词: molecular dynamics;    free energy;    reaction coordinate;   

DOI  :  10.3390/ijms140816058

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland