Breaking the conformational ensemble barrier: Ensemble structure modeling challenges in CASP15

Author:

Kryshtafovych Andriy1ORCID,Montelione Gaetano T.2ORCID,Rigden Daniel J.3ORCID,Mesdaghi Shahram34,Karaca Ezgi56ORCID,Moult John78

Affiliation:

1. Genome Center University of California, Davis Davis California USA

2. Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Sciences Rensselaer Polytechnic Institute Troy New York USA

3. Institute of Systems, Molecular, and Integrative Biology University of Liverpool Liverpool UK

4. Computational Biology Facility, MerseyBio University of Liverpool Liverpool UK

5. Izmir Biomedicine and Genome Center Izmir Turkey

6. Izmir International Biomedicine and Genome Institute Dokuz Eylul University Izmir Turkey

7. Institute for Bioscience and Biotechnology Research Rockville Maryland USA

8. Department of Cell Biology and Molecular Genetics University of Maryland College Park Maryland USA

Abstract

AbstractFor the first time, the 2022 CASP (Critical Assessment of Structure Prediction) community experiment included a section on computing multiple conformations for protein and RNA structures. There was full or partial success in reproducing the ensembles for four of the nine targets, an encouraging result. For protein structures, enhanced sampling with variations of the AlphaFold2 deep learning method was by far the most effective approach. One substantial conformational change caused by a single mutation across a complex interface was accurately reproduced. In two other assembly modeling cases, methods succeeded in sampling conformations near to the experimental ones even though environmental factors were not included in the calculations. An experimentally derived flexibility ensemble allowed a single accurate RNA structure model to be identified. Difficulties included how to handle sparse or low‐resolution experimental data and the current lack of effective methods for modeling RNA/protein complexes. However, these and other obstacles appear addressable.

Funder

Biotechnology and Biological Sciences Research Council

Publisher

Wiley

Subject

Molecular Biology,Biochemistry,Structural Biology

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. AlphaFold2 has more to learn about protein energy landscapes;2023-12-13

2. Critical assessment of methods of protein structure prediction (CASP)—Round XV;Proteins: Structure, Function, and Bioinformatics;2023-11-02

3. New prediction categories in CASP15;Proteins: Structure, Function, and Bioinformatics;2023-06-12

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