Minimalist models for protein folding and design.
Protein folding research during the past decade has emphasized the dominant role of native state topology in determining the speed and mechanism of folding for small proteins; this has been illustrated by simulations using minimalist protein models. The advantages of minimalist protein models lie in their ability to rapidly collect meaningful statistics about folding pathways and kinetics, their ease of characterization with coarse-grained order parameters and their concentration on the essential physics of the problem to connect with experimental observables for a target protein. The maturation of experimental protein folding has driven the need for more quantitative protein simulations to better understand the balance between sequence details and fold topology. In the past year, we have seen the emergence of more complex minimalist models, ranging from all-atom Gō potentials to coarse-grained bead models in which Gō interactions are replaced or supplemented by more physically motivated potentials. The reduced computational cost at the coarse-grained level of abstraction will potentially enable both folding studies on a genomic scale and systematic application in protein design.
Department of Bioengineering, University of California, Berkeley 94720, USA. TLHead-Gordon@lbl.gov
Teresa
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Head-Gordon
Scott
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Brown
D001426:Bacterial Proteins; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry; D015195:Drug Design; D004735:Energy Transfer; D008956:Models, Chemical; D009419:Nerve Tissue Proteins / Q000737:chemistry; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013314:Stress, Mechanical; D014867:Water / Q000737:chemistry*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C029152:G-substrate; C116593:L-protein, Peptococcus magnus; D009419:Nerve Tissue Proteins; D011506:Proteins; D012997:Solvents; D014867:Water