Assembly of a tetrameric alpha-helical bundle: computer simulations on an intermediate-resolution protein model.
Discontinuous molecular dynamics (DMD) simulation on an intermediate-resolution protein model is used to study the folding of an isolated, small model peptide to an amphipathic alpha-helix and the assembly of four of these model peptides into a four-helix bundle. A total of 129 simulations were performed on the isolated peptide, and 50 simulations were performed on the four-peptide system. Simulations efficiently sample conformational space allowing complete folding trajectories from random initial configurations to be observed within 15 min for the one-peptide system and within 15 h for the four-peptide system on a 500-MHz workstation. The native structures of both the alpha-helix and the four-helix bundle are consistent with experimental characterization studies and with results from previous simulations on these model peptides. In both the one- and four-peptide systems, the native state is achieved during simulations within an optimal temperature range, a phenomenon also observed experimentally. The ease with which our simulations yield reasonable estimates of folded structures demonstrates the power of the intermediate-resolution model developed for this work and the DMD algorithm and suggests that simulations of very long times and of multiprotein systems may be possible with this model.
Smith
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AV
Department of Chemical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, USA.
Hall
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CK
D000596:Amino Acids / Q000737:chemistry; D003198:Computer Simulation; D004735:Energy Transfer; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary
D000596:Amino Acids; D010455:Peptides; D011108:Polymers