Small angle X-ray scattering and cross-linking for data assisted protein structure prediction in CASP 12 with prospects for improved accuracy

Proteins
Tadeusz L OgorzalekKrzysztof Fidelis

Abstract

Experimental data offers empowering constraints for structure prediction. These constraints can be used to filter equivalently scored models or more powerfully within optimization functions toward prediction. In CASP12, Small Angle X-ray Scattering (SAXS) and Cross-Linking Mass Spectrometry (CLMS) data, measured on an exemplary set of novel fold targets, were provided to the CASP community of protein structure predictors. As solution-based techniques, SAXS and CLMS can efficiently measure states of the full-length sequence in its native solution conformation and assembly. However, this experimental data did not substantially improve prediction accuracy judged by fits to crystallographic models. One issue, beyond intrinsic limitations of the algorithms, was a disconnect between crystal structures and solution-based measurements. Our analyses show that many targets had substantial percentages of disordered regions (up to 40%) or were multimeric or both. Thus, solution measurements of flexibility and assembly support variations that may confound prediction algorithms trained on crystallographic data and expecting globular fully-folded monomeric proteins. Here, we consider the CLMS and SAXS data collected, the information in these ...Continue Reading

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Citations

Sep 27, 2019·Molecular Systems Biology·Marta L MendesJuri Rappsilber
Oct 12, 2019·Proteins·Davide SalaGaetano T Montelione
Aug 3, 2019·Proteins·Dmytro GuzenkoJose M Duarte
Jan 12, 2021·Computational and Structural Biotechnology Journal·Samantha J ZieglerYannick J Bomble
Aug 24, 2020·Current Opinion in Chemical Biology·Adam Belsom, Juri Rappsilber
Jan 31, 2020·Journal of Chemical Information and Modeling·Agnieszka S KarczyńskaCezary Czaplewski

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