Ligand screening by exoproteolysis and mass spectrometry in combination with computer modelling

Josep Villanueva, Gregorio Fernández-Ballester, Enrique Querol, Francesc X. Aviles, Luis Serrano

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12 Citations (Scopus)

Abstract

Here, we present a new approach for protein ligand screening based on the use of limited exoproteolysis coupled to MALDI-TOF mass spectrometry, combined with computational modelling and prediction of binding energies. As a test for this combined approach, we have screened a combinatorial library containing 8000 peptides (organized in 60 peptide samples) based on positional scanning format. This library is attached to a poly-Pro framework, and screened against the Abl-SH3 domain. The results obtained demonstrated the validity of the experimental and theoretical approaches in identifying better ligands and in rationalizing the changes in affinity. Exoproteolysis coupled to MALDI-TOF mass spectrometry could be used to screen complex libraries in a fast and efficient way. © 2003 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1039-1048
JournalJournal of Molecular Biology
Volume330
Issue number5
DOIs
Publication statusPublished - 25 Jul 2003

Keywords

  • Binding constant
  • Computer design
  • Ligand screening
  • Mass spectrometry
  • SH3 domain

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    Villanueva, J., Fernández-Ballester, G., Querol, E., Aviles, F. X., & Serrano, L. (2003). Ligand screening by exoproteolysis and mass spectrometry in combination with computer modelling. Journal of Molecular Biology, 330(5), 1039-1048. https://doi.org/10.1016/S0022-2836(03)00664-8