2025/05/20 by Stahl, Kolja, Warneke, Robert, Demann, Lorenz +5
#000 Informatik #500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften #AlphaFold-Multimer #Daten #Informationswissenschaft #Programme #Systeme::005 Computerprogrammierung #Wissen #allgemeine Werke::000 Informatik #crosslinking #machine learning #mass spectrometry #protein complexes #spectroscopy
paper · doi:10.14279/depositonce-22824
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 .