Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities

Abstract A preceding experiment suggested that a compound, which inhibits binding of the REST/NRSF segment to the cleft of a receptor protein mSin3B, can be a potential drug candidate to ameliorate many neuropathies. We have recently developed an enhanced conformational sampling method, genetic-algo...

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Autores principales:	Tomonori Hayami, Narutoshi Kamiya, Kota Kasahara, Takeshi Kawabata, Jun-ichi Kurita, Yoshifumi Fukunishi, Yoshifumi Nishimura, Haruki Nakamura, Junichi Higo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2898f8cc3360474e8e56e88ebf1a1694
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spelling	oai:doaj.org-article:2898f8cc3360474e8e56e88ebf1a16942021-12-02T17:05:12ZDifference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities10.1038/s41598-021-85612-92045-2322https://doaj.org/article/2898f8cc3360474e8e56e88ebf1a16942021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85612-9https://doaj.org/toc/2045-2322Abstract A preceding experiment suggested that a compound, which inhibits binding of the REST/NRSF segment to the cleft of a receptor protein mSin3B, can be a potential drug candidate to ameliorate many neuropathies. We have recently developed an enhanced conformational sampling method, genetic-algorithm-guided multi-dimensional virtual-system-coupled canonical molecular dynamics, and in the present study, applied it to three systems consisting of mSin3B and one of three compounds, sertraline, YN3, and acitretin. Other preceding experiments showed that only sertraline inhibits the binding of REST/NRSF to mSin3B. The current simulation study produced the spatial distribution of the compounds around mSin3B, and showed that sertraline and YN3 bound to the cleft of mSin3B with a high propensity, although acitretin did not. Further analyses of the simulation data indicated that only the sertraline–mSin3B complex produced a hydrophobic core similar to that observed in the molecular interface of the REST/NRSF-mSin3B complex: An aromatic ring of sertraline sunk deeply in the mSin3B’s cleft forming a hydrophobic core contacting to hydrophobic amino-acid residues located at the bottom of the cleft. The present study proposes a step to design a compound that inhibits competitively the binding of a ligand to its receptor.Tomonori HayamiNarutoshi KamiyaKota KasaharaTakeshi KawabataJun-ichi KuritaYoshifumi FukunishiYoshifumi NishimuraHaruki NakamuraJunichi HigoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomonori Hayami Narutoshi Kamiya Kota Kasahara Takeshi Kawabata Jun-ichi Kurita Yoshifumi Fukunishi Yoshifumi Nishimura Haruki Nakamura Junichi Higo Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities
description	Abstract A preceding experiment suggested that a compound, which inhibits binding of the REST/NRSF segment to the cleft of a receptor protein mSin3B, can be a potential drug candidate to ameliorate many neuropathies. We have recently developed an enhanced conformational sampling method, genetic-algorithm-guided multi-dimensional virtual-system-coupled canonical molecular dynamics, and in the present study, applied it to three systems consisting of mSin3B and one of three compounds, sertraline, YN3, and acitretin. Other preceding experiments showed that only sertraline inhibits the binding of REST/NRSF to mSin3B. The current simulation study produced the spatial distribution of the compounds around mSin3B, and showed that sertraline and YN3 bound to the cleft of mSin3B with a high propensity, although acitretin did not. Further analyses of the simulation data indicated that only the sertraline–mSin3B complex produced a hydrophobic core similar to that observed in the molecular interface of the REST/NRSF-mSin3B complex: An aromatic ring of sertraline sunk deeply in the mSin3B’s cleft forming a hydrophobic core contacting to hydrophobic amino-acid residues located at the bottom of the cleft. The present study proposes a step to design a compound that inhibits competitively the binding of a ligand to its receptor.
format	article
author	Tomonori Hayami Narutoshi Kamiya Kota Kasahara Takeshi Kawabata Jun-ichi Kurita Yoshifumi Fukunishi Yoshifumi Nishimura Haruki Nakamura Junichi Higo
author_facet	Tomonori Hayami Narutoshi Kamiya Kota Kasahara Takeshi Kawabata Jun-ichi Kurita Yoshifumi Fukunishi Yoshifumi Nishimura Haruki Nakamura Junichi Higo
author_sort	Tomonori Hayami
title	Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities
title_short	Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities
title_full	Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities
title_fullStr	Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities
title_full_unstemmed	Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities
title_sort	difference of binding modes among three ligands to a receptor msin3b corresponding to their inhibitory activities
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2898f8cc3360474e8e56e88ebf1a1694
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Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities

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