Year: 2024
Type: article
Abstract: Scarcity of structural and evolutionary information on protein complexes poses a challenge to deep learning-based structure modelling. We integrate experimental distance restraints obtained by crosslinking mass spectrometry (MS) into AlphaFold-Multimer, by extending AlphaLink to protein complexes. Integrating crosslinking MS data substantially improves modelling performance on challenging targets, by helping to identify interfaces, focusing sampling, and improving model selection. This extends to single crosslinks from whole-cell crosslinking MS, opening the possibility of whole-cell structural investigations driven by experimental data. We demonstrate this by revealing the molecular basis of iron homoeostasis in Bacillus subtilis.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: EXC 2008: Unifying Systems in Catalysis "UniSysCat", G2113968308, SFB 1565: Molekulare Mechanismen und Vernetzung von Prozessen der Genexpression, G3606019796, Modelling protein complexes with crosslinking mass spectrometry and deep learning, EXC 2002: Science of Intelligence (SCIoI), G6532450817, G814520914, Core Funding for the Wellcome Trust Centre for Cell Biology
OpenAlex ID: W4402364312