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Protein Structure Prediction in CASP13 Using AWSEM-Suite

  • Shikai Jin
    Shikai Jin
    Center for Theoretical Biological Physics  and  Department of Biosciences, Rice University, Houston, Texas 77005, United States
    More by Shikai Jin
  • Mingchen Chen
    Mingchen Chen
    Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United States
  • Xun Chen
    Xun Chen
    Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United States
    Department of Chemistry, Rice University, Houston, Texas 77005, United States
    More by Xun Chen
  • Carlos Bueno
    Carlos Bueno
    Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United States
    More by Carlos Bueno
  • Wei Lu
    Wei Lu
    Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United States
    Department of Physics, Rice University, Houston, Texas 77005, United States
    More by Wei Lu
  • Nicholas P. Schafer
    Nicholas P. Schafer
    Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005, United States
  • Xingcheng Lin
    Xingcheng Lin
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
  • José N. Onuchic
    José N. Onuchic
    Center for Theoretical Biological Physics  and 
    Department of Physics, Rice University, Houston, Texas 77005, United States
    Department of Chemistry, Rice University, Houston, Texas 77005, United States
    Department of Biosciences, Rice University, Houston, Texas 77005, United States
  • , and 
  • Peter G. Wolynes*
    Peter G. Wolynes
    Center for Theoretical Biological Physics  and 
    Department of Physics, Rice University, Houston, Texas 77005, United States
    Department of Chemistry, Rice University, Houston, Texas 77005, United States
    Department of Biosciences, Rice University, Houston, Texas 77005, United States
    *Email: [email protected]. Phone: (713) 348-4101.
Cite this: J. Chem. Theory Comput. 2020, 16, 6, 3977–3988
Publication Date (Web):May 12, 2020
https://doi.org/10.1021/acs.jctc.0c00188
Copyright © 2020 American Chemical Society

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    Abstract

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    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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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jctc.0c00188.

    • Qo values under different types of contacts and over different distance cutoffs; template and coevolutionary contact pairs for selected structures; contact map comparison of T0958-D1; quality of energy-based blind selection from prediction trajectory; free energy profiles of T0958; energy terms in different AWSEM force fields for T0958; correct contact versus length and sequence identity; ratio of correct contacts in different parts divided by domain length vs Qw value of each domain; Qw values vs secondary structure percent (PDF)

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    Cited By

    This article is cited by 11 publications.

    1. Luís Borges-Araújo, Ilias Patmanidis, Akhil P. Singh, Lucianna H. S. Santos, Adam K. Sieradzan, Stefano Vanni, Cezary Czaplewski, Sergio Pantano, Wataru Shinoda, Luca Monticelli, Adam Liwo, Siewert J. Marrink, Paulo C. T. Souza. Pragmatic Coarse-Graining of Proteins: Models and Applications. Journal of Chemical Theory and Computation 2023, 19 (20) , 7112-7135. https://doi.org/10.1021/acs.jctc.3c00733
    2. Mingchen Chen, Xun Chen, Shikai Jin, Wei Lu, Xingcheng Lin, Peter G. Wolynes. Protein Structure Refinement Guided by Atomic Packing Frustration Analysis. The Journal of Physical Chemistry B 2020, 124 (48) , 10889-10898. https://doi.org/10.1021/acs.jpcb.0c06719
    3. Wei Lu, Jixian Zhang, Weifeng Huang, Ziqiao Zhang, Xiangyu Jia, Zhenyu Wang, Leilei Shi, Chengtao Li, Peter G. Wolynes, Shuangjia Zheng. DynamicBind: predicting ligand-specific protein-ligand complex structure with a deep equivariant generative model. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-45461-2
    4. Maria I. Freiberger, Victoria Ruiz-Serra, Camila Pontes, Miguel Romero-Durana, Pablo Galaz-Davison, Cesar A. Ramírez-Sarmiento, Claudio D. Schuster, Marcelo A. Marti, Peter G. Wolynes, Diego U. Ferreiro, R. Gonzalo Parra, Alfonso Valencia. Local energetic frustration conservation in protein families and superfamilies. Nature Communications 2023, 14 (1) https://doi.org/10.1038/s41467-023-43801-2
    5. Yuda Chen, Shikai Jin, Mengxi Zhang, Yu Hu, Kuan-Lin Wu, Anna Chung, Shichao Wang, Zeru Tian, Yixian Wang, Peter G. Wolynes, Han Xiao. Unleashing the potential of noncanonical amino acid biosynthesis to create cells with precision tyrosine sulfation. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-33111-4
    6. Shikai Jin, Carlos Bueno, Wei Lu, Qian Wang, Mingchen Chen, Xun Chen, Peter G. Wolynes, Yang Gao. Computationally exploring the mechanism of bacteriophage T7 gp4 helicase translocating along ssDNA. Proceedings of the National Academy of Sciences 2022, 119 (32) https://doi.org/10.1073/pnas.2202239119
    7. Xun Chen, Wei Lu, Min-Yeh Tsai, Shikai Jin, Peter G. Wolynes. Exploring the folding energy landscapes of heme proteins using a hybrid AWSEM-heme model. Journal of Biological Physics 2022, 48 (1) , 37-53. https://doi.org/10.1007/s10867-021-09596-3
    8. Marco Giulini, Marta Rigoli, Giovanni Mattiotti, Roberto Menichetti, Thomas Tarenzi, Raffaele Fiorentini, Raffaello Potestio. From System Modeling to System Analysis: The Impact of Resolution Level and Resolution Distribution in the Computer-Aided Investigation of Biomolecules. Frontiers in Molecular Biosciences 2021, 8 https://doi.org/10.3389/fmolb.2021.676976
    9. Wei Lu, Carlos Bueno, Nicholas P. Schafer, Joshua Moller, Shikai Jin, Xun Chen, Mingchen Chen, Xinyu Gu, Aram Davtyan, Juan J. de Pablo, Peter G. Wolynes, . OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations. PLOS Computational Biology 2021, 17 (2) , e1008308. https://doi.org/10.1371/journal.pcbi.1008308
    10. Anna S. Kamenik, Philip H. Handle, Florian Hofer, Ursula Kahler, Johannes Kraml, Klaus R. Liedl. Polarizable and non-polarizable force fields: Protein folding, unfolding, and misfolding. The Journal of Chemical Physics 2020, 153 (18) https://doi.org/10.1063/5.0022135
    11. Shikai Jin, Mitchell D. Miller, Mingchen Chen, Nicholas P. Schafer, Xingcheng Lin, Xun Chen, George N. Phillips, Peter G. Wolynes. Molecular-replacement phasing using predicted protein structures from AWSEM-Suite. IUCrJ 2020, 7 (6) , 1168-1178. https://doi.org/10.1107/S2052252520013494

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