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  Predicting the Affinity of Peptides to Major Histocompatibility Complex Class II by Scoring Molecular Dynamics Simulations

Ochoa, R., Laio, A., & Cossio, P. (2019). Predicting the Affinity of Peptides to Major Histocompatibility Complex Class II by Scoring Molecular Dynamics Simulations. Journal of Chemical Information and Modeling, 59(8), 3464-3473. doi:10.1021/acs.jcim.9b00403.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-7A9A-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-AA38-E
Genre: Journal Article

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 Creators:
Ochoa, Rodrigo1, Author
Laio, Alessandro2, 3, Author
Cossio, Pilar1, 4, Author              
Affiliations:
1Biophysics of Tropical Diseases, Max Planck Tandem Group, University of Antioquia, Medellin, Colombia, ou_persistent22              
2International School for Advanced Studies (SISSA), Via Bonomea, Trieste, Italy, ou_persistent22              
3The Abdus Salam International Centre for Theoretical Physics (ICTP), Strada Costiera, Trieste, Italy, ou_persistent22              
4Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              

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 Abstract: Predicting the binding affinity of peptides able to interact with major histocompatibility complex (MHC) molecules is a priority for researchers working in the identification of novel vaccines candidates. Most available approaches are based on the analysis of the sequence of peptides of known experimental affinity. However, for MHC class II receptors, these approaches are not very accurate, due to the intrinsic flexibility of the complex. To overcome these limitations, we propose to estimate the binding affinity of peptides bound to an MHC class II by averaging the score of the configurations from finite-temperature molecular dynamics simulations. The score is estimated for 18 different scoring functions, and we explored the optimal manner for combining them. To test the predictions, we considered eight peptides of known binding affinity. We found that six scoring functions correlate with the experimental ranking of the peptides significantly better than the others. We then assessed a set of techniques for combining the scoring functions by linear regression and logistic regression. We obtained a maximum accuracy of 82% for the predicted sign of the binding affinity using a logistic regression with optimized weights. These results are potentially useful to improve the reliability of in silico protocols to design high-affinity binding peptides for MHC class II receptors.

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Language(s): eng - English
 Dates: 2019-05-132019-07-102019-08-26
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1021/acs.jcim.9b00403
 Degree: -

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Title: Journal of Chemical Information and Modeling
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 59 (8) Sequence Number: - Start / End Page: 3464 - 3473 Identifier: ISSN: 1549-9596
CoNE: https://pure.mpg.de/cone/journals/resource/954925465222