The success rate of processed predicted models in molecular replacement: implications for experimental phasing in the AlphaFold era.

Keegan, Ronan M ORCID: 0000-0002-9495-0431, Simpkin, Adam J ORCID: 0000-0003-1883-9376 and Rigden, Daniel J ORCID: 0000-0002-7565-8937 (2024) The success rate of processed predicted models in molecular replacement: implications for experimental phasing in the AlphaFold era. Acta crystallographica. Section D, Structural biology, 80 (Pt 11). pp. 766-779. ISSN 2059-7983, 2059-7983

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Official URL: https://doi.org/10.1107/s2059798324009380

Abstract

The availability of highly accurate protein structure predictions from AlphaFold2 (AF2) and similar tools has hugely expanded the applicability of molecular replacement (MR) for crystal structure solution. Many structures can be solved routinely using raw models, structures processed to remove unreliable parts or models split into distinct structural units. There is therefore an open question around how many and which cases still require experimental phasing methods such as single-wavelength anomalous diffraction (SAD). Here, this question is addressed using a large set of PDB depositions that were solved by SAD. A large majority (87%) could be solved using unedited or minimally edited AF2 predictions. A further 18 (4%) yield straightforwardly to MR after splitting of the AF2 prediction using Slice'N'Dice, although different splitting methods succeeded on slightly different sets of cases. It is also found that further unique targets can be solved by alternative modelling approaches such as ESMFold (four cases), alternative MR approaches such as ARCIMBOLDO and AMPLE (two cases each), and multimeric model building with AlphaFold-Multimer or UniFold (three cases). Ultimately, only 12 cases, or 3% of the SAD-phased set, did not yield to any form of MR tested here, offering valuable hints as to the number and the characteristics of cases where experimental phasing remains essential for macromolecular structure solution.

Item Type:	Article
Uncontrolled Keywords:	Proteins, Crystallography, X-Ray, Protein Conformation, Protein Folding, Models, Molecular, Software, Databases, Protein
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	01 Nov 2024 10:35
Last Modified:	09 Dec 2024 11:02
DOI:	10.1107/s2059798324009380
Open Access URL:	https://doi.org/10.1107/S2059798324009380
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3186997