Protein structure prediction with in-cell photo-crosslinking mass spectrometry and deep learning.

ABSTRACT: While AlphaFold2 can predict accurate protein structures from the primary sequence, challenges remain for proteins that undergo conformational changes or for which few homologous sequences are known. Here we introduce AlphaLink, a modified version of the AlphaFold2 algorithm that incorporates experimental distance restraint information into its network architecture. By employing sparse experimental contacts as anchor points, AlphaLink improves on the performance of AlphaFold2 in predicting challenging targets. We confirm this experimentally by using the noncanonical amino acid photo-leucine to obtain information on residue-residue contacts inside cells by crosslinking mass spectrometry. The program can predict distinct conformations of proteins on the basis of the distance restraints provi

SUBMITTER: Stahl K 

PROVIDER: S-EPMC10713450 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature