Abstract
The AlphaFold2 results in the 14th edition of Critical Assessment of Structure Prediction (CASP14) showed that accurate (low root-mean-square deviation) insilico models of protein structure domains are on the horizon, whether or not the protein is related to known structures through high-coverage sequence similarity. As highly accurate models become available, generated by harnessing the power of correlated mutations and deep learning, one of the aspects of structural biology to be impacted will be methods of phasing in crystallography. Here, the data from CASP14 are used to explore the prospects for changes in phasing methods, and in particular to explore the prospects for molecular-replacement phasing using in silico models.
Highlights
The quality of a model for phasing a crystal structure by molecular replacement, for a given diffraction resolution limit, depends on the root-mean-square deviation (r.m.s.d.) of the model to the target structure and the fraction of the total scattering that it represents
We have previously shown that the expected LLG’ (eLLG) for each reflection hkl can be calculated from the A parameter (Read, 1986): eLLGhkl
CASP classifies the targets by modelling difficulty in four categories: free modelling (FM), template-based modelling (TBM-easy and TBM-hard) and structures on the boundary between free modelling and template-based modelling (FM/ TBM)
Summary
The quality of a model for phasing a crystal structure by molecular replacement, for a given diffraction resolution limit, depends on the root-mean-square deviation (r.m.s.d.) of the model to the target structure and the fraction of the total scattering (fm) that it represents. When the experimental data extend to lower than $2.2 A In further developments, AMPLE has been extended to use resolution the models required for molecular replacement structure predictions from the GREMLIN and PconsFam must represent, to at least some degree, the fold of the target databases (Simpkin et al, 2019). We use Rosetta, extended to gued by the Critical Assessment of Structure Prediction, include a term for fit to the electron density (DiMaio, 2013), to CASP) generally increased (rather than decreased, as was the rank putative molecular-replacement solutions and to rebuild aim) the r.m.s.d. to the target. Show that template-based modelling improved models for molecular replacement From this CASP came the first case in which an in silico structure prediction for a natural 2. The AlphaFold model for T1064 has been used to solve the SARS-CoV-2 ORF8 structure retrospectively by molecular replacement (Flower & Hurley, 2021)
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