Protein Structure Prediction in CASP13 Using AWSEM-Suite
- Shikai Jin
Shikai JinCenter for Theoretical Biological Physics and Department of Biosciences, Rice University, Houston, Texas 77005, United StatesMore by Shikai Jin
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- Mingchen Chen
Mingchen ChenCenter for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United StatesMore by Mingchen Chen
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- Xun Chen
Xun ChenCenter for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United StatesDepartment of Chemistry, Rice University, Houston, Texas 77005, United StatesMore by Xun Chen
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- Carlos Bueno
Carlos BuenoCenter for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United StatesMore by Carlos Bueno
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- Wei Lu
Wei LuCenter for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United StatesDepartment of Physics, Rice University, Houston, Texas 77005, United StatesMore by Wei Lu
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- Nicholas P. Schafer
Nicholas P. SchaferCenter for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United StatesMore by Nicholas P. Schafer
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- Xingcheng Lin
Xingcheng LinDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United StatesMore by Xingcheng Lin
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- José N. Onuchic
José N. OnuchicCenter for Theoretical Biological Physics andDepartment of Physics, Rice University, Houston, Texas 77005, United StatesDepartment of Chemistry, Rice University, Houston, Texas 77005, United StatesDepartment of Biosciences, Rice University, Houston, Texas 77005, United StatesMore by José N. Onuchic
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- Peter G. Wolynes*
Peter G. Wolynes*Email: [email protected]. Phone: (713) 348-4101.Center for Theoretical Biological Physics andDepartment of Physics, Rice University, Houston, Texas 77005, United StatesDepartment of Chemistry, Rice University, Houston, Texas 77005, United StatesDepartment of Biosciences, Rice University, Houston, Texas 77005, United StatesMore by Peter G. Wolynes
Abstract
Recently several techniques have emerged that significantly enhance the quality of predictions of protein tertiary structures. In this study, we describe the performance of AWSEM-Suite, an algorithm that incorporates template-based modeling and coevolutionary restraints with a realistic coarse-grained force field, AWSEM. With its roots in neural networks, AWSEM contains both physical and bioinformatical energies that have been optimized using energy landscape theory. AWSEM-Suite participated in CASP13 as a server predictor and generated reliable predictions for most targets. AWSEM-Suite ranked eighth in both the free-modeling category and the hard-to-model category and in one case provided the best submitted prediction. Here we critically discuss the prediction performance of AWSEM-Suite using several examples from different categories in CASP13. Structure prediction tests on these selected targets, two of them being hard-to-model targets, show that AWSEM-Suite can achieve high-resolution structure prediction after incorporating both template guidances and coevolutionary restraints even when homology is weak. For targets with reliable templates (template-easy category), introducing coevolutionary restraints sometimes damages the overall quality of the predictions. Free energy profile analyses demonstrate, however, that the incorporations of both of these evolutionarily informed terms effectively increase the funneling of the landscape toward native-like structures while still allowing sufficient flexibility to correct for discrepancies between the correct target structure and the provided guidance. In contrast to other predictors that are exclusively oriented toward structure prediction, the connection of AWSEM-Suite to a statistical mechanical basis and affiliated molecular dynamics and importance sampling simulations makes it suitable for functional explorations.
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