Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations.
Biomolecules often undergo large-amplitude motions when they bind or release other molecules. Unlike macroscopic machines, these biomolecular machines can partially disassemble (unfold) and then reassemble (fold) during such transitions. Here we put forward a minimal structure-based model, the "multiple-basin model," that can directly be used for molecular dynamics simulation of even very large biomolecular systems so long as the endpoints of the conformational change are known. We investigate the model by simulating large-scale motions of four proteins: glutamine-binding protein, S100A6, dihydrofolate reductase, and HIV-1 protease. The mechanisms of conformational transition depend on the protein basin topologies and change with temperature near the folding transition. The conformational transition rate varies linearly with driving force over a fairly large range. This linearity appears to be a consequence of partial unfolding during the conformational transition.
Okazaki
Kei-ichi
K
Graduate School of Natural Science and Technology, Kobe University, Kobe 657-8501, Japan.
Koga
Nobuyasu
N
Takada
Shoji
S
Onuchic
Jose N
JN
Wolynes
Peter G
PG
D002352:Carrier Proteins / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000737:chemistry; D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry; D006801:Humans; D008962:Models, Theoretical; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C037853:glutamine transport proteins; C055351:S100A6 protein, human; D013762:Tetrahydrofolate Dehydrogenase; D016333:HIV Protease