Evidence map›Paper›PMID 38351232›Full record

ArticleJournal of molecular modeling2024

Exploring the binding mechanism of a small molecular Hsp70-Bim PPI inhibitor through molecular dynamic simulation.

Xin Li, Yuying Wang, Maojun Jiang, Fangkui Yin, Hong Zhang, Linjie Yuan, Jingjing Liu, Xingyu Wang, Ziqian Wang, Zhichao Zhang

Abstract read
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Article in Journal of molecular modeling, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Xin LiCancer Hospital of Dalian University of Technology, School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.ORCID http://orcid.org/0000-0002-3536-1522
Yuying WangCancer Hospital of Dalian University of Technology, School of Life Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Maojun JiangCancer Hospital of Dalian University of Technology, School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.
Fangkui YinCancer Hospital of Dalian University of Technology, School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.
Hong ZhangCancer Hospital of Dalian University of Technology, School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.
Linjie YuanCancer Hospital of Dalian University of Technology, School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.
Jingjing LiuCancer Hospital of Dalian University of Technology, School of Life Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Xingyu WangCancer Hospital of Dalian University of Technology, School of Life Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Ziqian WangCancer Hospital of Dalian University of Technology, School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China. wangziqian@dlut.edu.cn.
Zhichao ZhangCancer Hospital of Dalian University of Technology, School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China. zczhang@dlut.edu.cn.ORCID http://orcid.org/0000-0002-2774-2384

Funding

National Natural Science Foundation of China 82273778the Fundamental Research Funds for the Central University DUT22YG223
6 · The paper itself

Abstract

contextThe interface of Hsp70-Bim protein-protein interaction (PPI) has been identified as a specific target for Chronic Myeloid Leukemia (CML) therapy and the specific inhibitors were developed to exhibit in vivo anti-leukemia activities. Herein, we explored the binding mechanism of a Hsp70-Bim inhibitor, 6-(cyclohexylthio)-3-((2-morpholinoethyl) amino)-1-oxo-1H-phenalene-2-carbonitrile (S1g-6), to Hsp70 at the atomic level by MD simulation. TYR-149, THR-222, ALA-223, and GLY-224 on Hsp70 were identified as four key residues that contribute to Hsp70/S1g-6 complex. Moreover, the site mutation validation demonstrated the TYR-149 of Hsp70 is a "hot-spot" in the Hsp70-Bim PPI interface. These results could benefit the design of further inhibitors to occupy the Bim binding site on the Hsp70 surface.

methodsThe binding mechanism of S1g-6 and Hsp70 was predicted through the molecular dynamics (MD) method by Gromacs-2021.3. The MD simulation was performed with 100-ps NVT and 100-ps NPT ensemble, and the force field was chosen as the Charmm36 force field. The temperature was set as 300 K, the time step was 2 fs and the total MD simulation time was 500 ns.

Indexed as

HSP70 Heat-Shock ProteinsMolecular Dynamics SimulationBase SequenceBinding SitesProtein DomainsHSP70 Heat-Shock ProteinsHeat shock protein 70Hot-spotHsp70/Bim heterodimersMolecular Dynamic simulationProtein–Protein Interaction

Identifiers

PMID38351232

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.