Contact Order and Ab Initio Protein Structure Prediction (1937)

Content Provider	CiteSeerX
Author	Ingo, Richard Bonneau Ruczinski, Ingo Tsai, Jerry Baker, David
Description	Although much of the motivation for experimental studies of protein folding is to obtain insights for improving protein structure prediction, there has been relatively little connection between experimental protein folding studies and computational structural prediction work in recent years. In the present study, we show that the relationship between protein folding rates and the contact order (CO) of the native structure has implications for ab initio protein structure prediction. Rosetta ab initio folding simulations produce a dearth of high CO structures and an excess of low CO structures, as expected if the computer simulations mimic to some extent the actual folding process. Consistent with this, the majority of failures in ab initio prediction in the CASP4 (critical assessment of structure prediction) experiment involved high CO structures likely to fold much more slowly than the lower CO structures for which reasonable predictions were made. This bias against high CO structures can be partially alleviated by performing large numbers of additional simulations, selecting out the higher CO structures, and eliminating the very low CO structures; this leads to a modest improvement in prediction quality. More significant improvements in predictions for proteins with complex topologies may be possible following significant increases in high-performance computing power, which will be required for thoroughly sampling high CO conformations (high CO proteins can take six orders of magnitude longer to fold than low CO proteins). Importantly for such a strategy, simulations performed for high CO structures converge much less strongly than those for low CO structures, and hence, lack of simulation convergence can indicate the need for improved sampling of high ...
File Format	PDF
Journal	Protein Sci
Language	English
Publisher Date	1937-01-01
Access Restriction	Open
Subject Keyword	Actual Folding Process Complex Topology Native Structure Experimental Protein Improved Sampling Magnitude Longer Critical Assessment Experimental Study Additional Simulation Contact Order Low Co Protein High Co Protein Ab Initio Prediction Computer Simulation Modest Improvement Present Study Co Structure Structure Prediction Reasonable Prediction Rosetta Ab Initio High Co Structure Computational Structural Prediction Work High Co Protein Structure Prediction Low Co Structure Significant Improvement Protein Folding Significant Increase Simulation Convergence Large Number Prediction Quality Recent Year Ab Initio Protein Structure Prediction High Co Conformation Low Co Little Connection
Content Type	Text
Resource Type	Article