Dataset Information

AlphaLink: bringing protein structure prediction in situ with in-cell photo-crosslinking mass spectrometry, crosslinking mass spectrometry, XL-MS,

ABSTRACT: The protein structure prediction problem has been revolutionised by AlphaFold2, an algorithm that uses neural networks and evolutionary information to predict accurate models from the primary sequence. However, some proteins remain difficult to predict. Moreover, proteins are dynamic entities that exist in complex environments in vivo. Here, we use the noncanonical amino acid Photo-Leucine to obtain information on residue-residue contacts inside cells by crosslinking mass spectrometry. We then introduce AlphaLink, a modified version of the AlphaFold2 algorithm that synergistically incorporates experimental distance restraint information into its network architecture. AlphaLink improves on the performance of AlphaFold2 in predicting challenging targets in both synthetic and real-world scenarios by employing sparse experimental contacts as anchor points. The program can predict individual conformations of proteins based on the distance restraints provided. The noise-tolerant framework presented here for integrating data in protein structure prediction opens a path to accurate characterisation of protein structures from in-cell data.

ORGANISM(S): Escherichia Coli

SUBMITTER: Juri Rappsilber

PROVIDER: PXD036833 | JPOST Repository | Wed Feb 22 00:00:00 GMT 2023

REPOSITORIES: jPOST

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Dataset's files

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			Action	DRS
	recal_B190214_02_Lumos_TD_IN_120_Ecoli_photoAA_membrane_SCX16_SEC6.mgf	Mgf
	recal_B190214_03_Lumos_TD_IN_120_Ecoli_photoAA_membrane_SCX16_SEC7.mgf	Mgf
	recal_B190214_04_Lumos_TD_IN_120_Ecoli_photoAA_membrane_SCX16_SEC8.mgf	Mgf
	recal_B190214_05_Lumos_TD_IN_120_Ecoli_photoAA_membrane_SCX16_SEC9.mgf	Mgf
	recal_B190214_06_Lumos_TD_IN_120_Ecoli_photoAA_membrane_SCX16_SEC10.mgf	Mgf

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Publications

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

Stahl Kolja K Graziadei Andrea A Dau Therese T Brock Oliver O Rappsilber Juri J

Nature biotechnology 20230320 12

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 chall ...[more]

PMID: 36941363

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