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231225s2021 xx |||||o 00| ||eng c |
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|a 10.1002/jcc.26516
|2 doi
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|a pubmed24n1077.xml
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|a (DE-627)NLM32311508X
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|a (NLM)33755222
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
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|a Higo, Junichi
|e verfasserin
|4 aut
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|a Generalized-ensemble method study
|b A helix-mimetic compound inhibits protein-protein interaction by long-range and short-range intermolecular interactions
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|c 2021
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 18.10.2021
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|a Date Revised 18.10.2021
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2021 Wiley Periodicals LLC.
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|a A heterocyclic compound mS-11 is a helix-mimetic designed to inhibit binding of an intrinsic disordered protein neural restrictive silence factor/repressor element 1 silencing factor (NRSF/REST) to a receptor protein mSin3B. We apply a generalized ensemble method, multi-dimensional virtual-system coupled molecular dynamics developed by ourselves recently, to a system consisting of mS-11 and mSin3B, and obtain a thermally equilibrated distribution, which is comprised of the bound and unbound states extensively. The lowest free-energy position of mS-11 coincides with the NRSF/REST position in the experimentally-determined NRSF/REST-mSin3B complex. Importantly, the molecular orientation of mS-11 is ordering in a wide region around mSin3B. The resultant binding scenario is: When mS-11 is distant from the binding site of mSin3B, mS-11 descends the free-energy slope toward the binding site maintaining the molecular orientation to be advantageous for binding. Then, finally a long and flexible hydrophobic sidechain of mS-11 fits into the binding site, which is the lowest-free-energy complex structure inhibiting NRSF/REST binding to mSin3B
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a enhanced sampling
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|a free-energy landscape
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|a generalized ensemble
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|a inhibition
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|a molecular binding
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|a Heterocyclic Compounds, 2-Ring
|2 NLM
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| 650 |
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|a MS-11 compound
|2 NLM
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| 650 |
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|a Repressor Proteins
|2 NLM
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| 650 |
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|a Sin3b protein, mouse
|2 NLM
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| 700 |
1 |
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|a Takashima, Hajime
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Fukunishi, Yoshifumi
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yoshimori, Atsushi
|e verfasserin
|4 aut
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| 773 |
0 |
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|i Enthalten in
|t Journal of computational chemistry
|d 1984
|g 42(2021), 14 vom: 30. Mai, Seite 956-969
|w (DE-627)NLM098138448
|x 1096-987X
|7 nnns
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| 773 |
1 |
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|g volume:42
|g year:2021
|g number:14
|g day:30
|g month:05
|g pages:956-969
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|u http://dx.doi.org/10.1002/jcc.26516
|3 Volltext
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|d 42
|j 2021
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|c 05
|h 956-969
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