title: Transition pathway and its free-energy profile: a protocol for protein folding simulations.
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.
authors.affiliation: Korea Research Institute of Standards and Science, Daejon 305-340, Korea. ihlee@kriss.re.kr
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Lee
authors.forename: Seung-Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Lee
mesh_terms: D004744:Enkephalin, Methionine / Q000032:analysis* / Q000378:metabolism*; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D004744:Enkephalin, Methionine
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