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

Kryshtafovych A., Montelione G. T., Rigden D. J., Mesdaghi S., Karaca Erek E., Moult J.

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/prot.26584
  • Dergi Adı: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Food Science & Technology Abstracts, INSPEC, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: AlphaFold, CASP, conformational ensemble, protein structure, RNA structure
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

For 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.