Cargando…

Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors

Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Fengqi, Tanaka, Shigenori, Watanabe, Hirofumi, Shimane, Yasuhiro, Iwasawa, Misako, Ohishi, Kazue, Maruyama, Tadashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977229/
https://www.ncbi.nlm.nih.gov/pubmed/29751531
http://dx.doi.org/10.3390/v10050236
_version_ 1783327334939492352
author Xu, Fengqi
Tanaka, Shigenori
Watanabe, Hirofumi
Shimane, Yasuhiro
Iwasawa, Misako
Ohishi, Kazue
Maruyama, Tadashi
author_facet Xu, Fengqi
Tanaka, Shigenori
Watanabe, Hirofumi
Shimane, Yasuhiro
Iwasawa, Misako
Ohishi, Kazue
Maruyama, Tadashi
author_sort Xu, Fengqi
collection PubMed
description Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors. As predicted from previously reported experiments, some important amino-acid residues of MVH were shown to be common but others were specific to interactions with the three receptors. Particularly, some of the (non-polar) hydrophobic residues of MVH were found to be attractively interacting with multiple receptors, thus indicating the importance of the hydrophobic pocket for intermolecular interactions (especially in the case of Nectin-4). In contrast, the electrostatic interactions tended to be used for specific molecular recognition. Furthermore, we carried out FMO calculations for in silico experiments of amino acid mutations, finding reasonable agreements with virological experiments concerning the substitution effect of residues. Thus, the present study demonstrates that the electron-correlated FMO method is a powerful tool to search exhaustively for amino acid residues that contribute to interactions with receptor molecules. It is also applicable for designing inhibitors of MVH and engineered MVs for cancer therapy.
format Online
Article
Text
id pubmed-5977229
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-59772292018-06-01 Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors Xu, Fengqi Tanaka, Shigenori Watanabe, Hirofumi Shimane, Yasuhiro Iwasawa, Misako Ohishi, Kazue Maruyama, Tadashi Viruses Article Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors. As predicted from previously reported experiments, some important amino-acid residues of MVH were shown to be common but others were specific to interactions with the three receptors. Particularly, some of the (non-polar) hydrophobic residues of MVH were found to be attractively interacting with multiple receptors, thus indicating the importance of the hydrophobic pocket for intermolecular interactions (especially in the case of Nectin-4). In contrast, the electrostatic interactions tended to be used for specific molecular recognition. Furthermore, we carried out FMO calculations for in silico experiments of amino acid mutations, finding reasonable agreements with virological experiments concerning the substitution effect of residues. Thus, the present study demonstrates that the electron-correlated FMO method is a powerful tool to search exhaustively for amino acid residues that contribute to interactions with receptor molecules. It is also applicable for designing inhibitors of MVH and engineered MVs for cancer therapy. MDPI 2018-05-03 /pmc/articles/PMC5977229/ /pubmed/29751531 http://dx.doi.org/10.3390/v10050236 Text en © 2018 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
Xu, Fengqi
Tanaka, Shigenori
Watanabe, Hirofumi
Shimane, Yasuhiro
Iwasawa, Misako
Ohishi, Kazue
Maruyama, Tadashi
Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors
title Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors
title_full Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors
title_fullStr Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors
title_full_unstemmed Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors
title_short Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors
title_sort computational analysis of the interaction energies between amino acid residues of the measles virus hemagglutinin and its receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977229/
https://www.ncbi.nlm.nih.gov/pubmed/29751531
http://dx.doi.org/10.3390/v10050236
work_keys_str_mv AT xufengqi computationalanalysisoftheinteractionenergiesbetweenaminoacidresiduesofthemeaslesvirushemagglutininanditsreceptors
AT tanakashigenori computationalanalysisoftheinteractionenergiesbetweenaminoacidresiduesofthemeaslesvirushemagglutininanditsreceptors
AT watanabehirofumi computationalanalysisoftheinteractionenergiesbetweenaminoacidresiduesofthemeaslesvirushemagglutininanditsreceptors
AT shimaneyasuhiro computationalanalysisoftheinteractionenergiesbetweenaminoacidresiduesofthemeaslesvirushemagglutininanditsreceptors
AT iwasawamisako computationalanalysisoftheinteractionenergiesbetweenaminoacidresiduesofthemeaslesvirushemagglutininanditsreceptors
AT ohishikazue computationalanalysisoftheinteractionenergiesbetweenaminoacidresiduesofthemeaslesvirushemagglutininanditsreceptors
AT maruyamatadashi computationalanalysisoftheinteractionenergiesbetweenaminoacidresiduesofthemeaslesvirushemagglutininanditsreceptors