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Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences

The affinity of different drug-like ligands to multiple protein targets reflects general chemical–biological interactions. Computational methods estimating such interactions analyze the available information about the structure of the targets, ligands, or both. Prediction of protein–ligand interacti...

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Detalles Bibliográficos
Autores principales: Karasev, Dmitry, Sobolev, Boris, Lagunin, Alexey, Filimonov, Dmitry, Poroikov, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981593/
https://www.ncbi.nlm.nih.gov/pubmed/31861473
http://dx.doi.org/10.3390/ijms21010024
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author Karasev, Dmitry
Sobolev, Boris
Lagunin, Alexey
Filimonov, Dmitry
Poroikov, Vladimir
author_facet Karasev, Dmitry
Sobolev, Boris
Lagunin, Alexey
Filimonov, Dmitry
Poroikov, Vladimir
author_sort Karasev, Dmitry
collection PubMed
description The affinity of different drug-like ligands to multiple protein targets reflects general chemical–biological interactions. Computational methods estimating such interactions analyze the available information about the structure of the targets, ligands, or both. Prediction of protein–ligand interactions based on pairwise sequence alignment provides reasonable accuracy if the ligands’ specificity well coincides with the phylogenic taxonomy of the proteins. Methods using multiple alignment require an accurate match of functionally significant residues. Such conditions may not be met in the case of diverged protein families. To overcome these limitations, we propose an approach based on the analysis of local sequence similarity within the set of analyzed proteins. The positional scores, calculated by sequence fragment comparisons, are used as input data for the Bayesian classifier. Our approach provides a prediction accuracy comparable or exceeding those of other methods. It was demonstrated on the popular Gold Standard test sets, presenting different sequence heterogeneity and varying from the group, including different protein families to the more specific groups. A reasonable prediction accuracy was also found for protein kinases, displaying weak relationships between sequence phylogeny and inhibitor specificity. Thus, our method can be applied to the broad area of protein–ligand interactions.
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spelling pubmed-69815932020-02-03 Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences Karasev, Dmitry Sobolev, Boris Lagunin, Alexey Filimonov, Dmitry Poroikov, Vladimir Int J Mol Sci Article The affinity of different drug-like ligands to multiple protein targets reflects general chemical–biological interactions. Computational methods estimating such interactions analyze the available information about the structure of the targets, ligands, or both. Prediction of protein–ligand interactions based on pairwise sequence alignment provides reasonable accuracy if the ligands’ specificity well coincides with the phylogenic taxonomy of the proteins. Methods using multiple alignment require an accurate match of functionally significant residues. Such conditions may not be met in the case of diverged protein families. To overcome these limitations, we propose an approach based on the analysis of local sequence similarity within the set of analyzed proteins. The positional scores, calculated by sequence fragment comparisons, are used as input data for the Bayesian classifier. Our approach provides a prediction accuracy comparable or exceeding those of other methods. It was demonstrated on the popular Gold Standard test sets, presenting different sequence heterogeneity and varying from the group, including different protein families to the more specific groups. A reasonable prediction accuracy was also found for protein kinases, displaying weak relationships between sequence phylogeny and inhibitor specificity. Thus, our method can be applied to the broad area of protein–ligand interactions. MDPI 2019-12-18 /pmc/articles/PMC6981593/ /pubmed/31861473 http://dx.doi.org/10.3390/ijms21010024 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Karasev, Dmitry
Sobolev, Boris
Lagunin, Alexey
Filimonov, Dmitry
Poroikov, Vladimir
Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences
title Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences
title_full Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences
title_fullStr Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences
title_full_unstemmed Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences
title_short Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences
title_sort prediction of protein–ligand interaction based on the positional similarity scores derived from amino acid sequences
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981593/
https://www.ncbi.nlm.nih.gov/pubmed/31861473
http://dx.doi.org/10.3390/ijms21010024
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