Extending the Horizon: Multiscale Simulation of Proteins

Computer simulations of proteins have become a common tool for complementing structural information from experiment. Simulations can provide detailed insight into dynamic and energetic aspects of protein structures ranging from minor structural fluctuations to protein folding. Furthermore, computational modeling methods may also be used to predict protein structures in part or as a whole in the absence of suitable experimental data. Successful applications of such methods have followed increasingly realistic model representations, but are limited by the relatively short time scales and/or small system sizes that can be simulated. A new, multiscale modeling strategy will be presented that addresses these limitations and allows the modeling of much larger systems and over much longer time scales. In this approach approximate low-resolution models are used for fast sampling and combined with models in atomic detail that provide a more accurate energetic description. The efficiency of all-atom models is increased further with a new, recently improved continuum solvation description that replaces the need for explicit solvent molecules. Applications of such a multiscale modeling approach to the prediction of protein structures are discussed. Examples are presented for the modeling of missing loops in the context of known protein structures as well as for the prediction of complete proteins from the community-wide structure prediction experiment CASP5.

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