Modeling Flexible Protein Structure With AlphaFold2 and Crosslinking Mass Spectrometry.

ABSTRACT: We propose a pipeline that combines AlphaFold2 (AF2) and crosslinking mass spectrometry (XL-MS) to model the structure of proteins with multiple conformations. The pipeline consists of two main steps: ensemble generation using AF2 and conformer selection using XL-MS data. For conformer selection, we developed two scores-the monolink probability score (MP) and the crosslink probability score (XLP)-both of which are based on residue depth from the protein surface. We benchmarked MP and XLP on a large dataset of decoy protein structures and showed that our scores outperform previously developed scores. We then tested our methodology on three proteins having an open and closed conformation in the Protein Data Bank: Complement component 3 (C3), luciferase, and glutamine-binding periplasmic prot

SUBMITTER: Manalastas-Cantos K 

PROVIDER: S-EPMC10884514 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature