title: Predicting order of conformational changes during protein conformational transitions using an interpolated elastic network model.
abstract: The decryption of sequence of structural events during protein conformational transitions is essential to a detailed understanding of molecular functions of various biological nanomachines. Coarse-grained models have proven useful by allowing highly efficient simulations of protein conformational dynamics. By combining two coarse-grained elastic network models constructed based on the beginning and end conformations of a transition, we have developed an interpolated elastic network model to generate a transition pathway between the two protein conformations. For validation, we have predicted the order of local and global conformational changes during key ATP-driven transitions in three important biological nanomachines (myosin, F(1) ATPase and chaperonin GroEL). We have found that the local conformational change associated with the closing of active site precedes the global conformational change leading to mechanical motions. Our finding is in good agreement with the distribution of intermediate experimental structures, and it supports the importance of local motions at active site to drive or gate various conformational transitions underlying the workings of a diverse range of biological nanomachines.
authors.affiliation: Department of Physics, University at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekpinar
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002417:Cattle; D018834:Chaperonin 60 / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D013816:Thermodynamics
chemical_list: D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D011506:Proteins; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D009218:Myosins