PXD046392-2

PXD046392 is an original dataset announced via ProteomeXchange.

Title	Modeling flexible protein structure with AlphaFold2 and cross-linking mass spectrometry
Description	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. 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 protein (QBP), first generating ensembles using AF2, which were then screened for the open and closed conformations using experimental XL-MS data. In five out of six cases, the most accurate model within the AF2 ensembles – or a conformation within 1 Å of this model – was identified using crosslinks, as assessed through the XLP score. In the remaining case, only the monolinks (assessed through the MP score) successfully identified the open conformation of QBP. This serves as a compelling proof-of-concept for the effectiveness of monolinks. In contrast, the AF2 assessment score (pTM) was only able to identify the most accurate conformation in two out of six cases. Our results highlight the complementarity of AF2 with experimental methods like XL-MS, with the MP and XLP scores providing reliable metrics to assess the quality of the predicted models.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:42:28.441.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD046392
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kish Adoni
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-25 09:15:32	ID requested
1	2024-05-24 02:04:04	announced
⏵ 2	2024-10-22 06:42:34	announced	2024-10-22: Updated project metadata.

10.6019/PXD046392;

10.1016/j.mcpro.2024.100724;

Manalastas-Cantos K, Adoni KR, Pfeifer M, M, ä, rtens B, Gr, ü, newald K, Thalassinos K, Topf M, Modeling Flexible Protein Structure With AlphaFold2 and Crosslinking Mass Spectrometry. Mol Cell Proteomics, 23(3):100724(2024) [pubmed]

submitter keyword: Crosslinks,Monolinks, AlphaFold2, IDR, flexible protein

Konstantinos Thalassinos
contact affiliation	1. University College London 2. Birkbeck
contact email	k.thalassinos@ucl.ac.uk
lab head
Kish Adoni
contact affiliation	University College London
contact email	kish.95@live.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD046392

PRIDE project URI

• PRIDE
  1. PXD046392
     1. Label: PRIDE project
     2. Name: Modeling flexible protein structure with AlphaFold2 and cross-linking mass spectrometry