Virtual screening and molecular dynamics simulation of natural compounds as potential inhibitors of serine/threonine kinase 16 for anticancer drug discovery.

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-07-20 DOI:10.1007/s11030-024-10931-8
Dhurgham Al-Fahad, G Ropón-Palacios, Damilola A Omoboyowa, Gagandeep Singh, Rajesh B Patil
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Abstract

Serine/threonine kinase 16 (STK 16) is involved in many facets of cellular regulation; activation of STK 16 plays a crucial role in the migration of cancer cells. Therefore, it is a novel target for the discovery of anticancer agents. Herein, virtual screening and dynamics simulation were used to screen a large library of natural compounds against STK 16 using Schrodinger suit 2021-2 and GROMACS 2021.6. The results predicted five molecules with high binding affinity against the target, with NPC132329 (Arcyriaflavin C) and NPC160898 having higher binding affinity and molecular mechanics generalized born surface area (MM/GBSA), suggesting that it is better than the standard inhibitor. The molecular dymanics (MD) simulation studies showed that the STK 16-NPC132329 complex has the lowest root mean square deviation, and STK 16-NPC160898 was the most stable compared with the standard drug and selective STK 16 inhibitor. The minimal fluctuation was observed in the STK 16-NPC132329 and STK 16-NPC160898 complexes based on the root mean square fluctuation trajectory with NPC132329 and NPC160898 forming 2 and 3 hydrogen bonds respectively with the amino acid residue of the target's binding site. Overall, NPC132329 and NPC160898 are better STK 16 inhibitors than the standard drug and selective inhibitor, which can be further studied to discover novel anticancer drugs.

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将天然化合物作为丝氨酸/苏氨酸激酶 16 的潜在抑制剂进行虚拟筛选和分子动力学模拟,以发现抗癌药物。
丝氨酸/苏氨酸激酶 16(STK 16)参与细胞调控的许多方面;STK 16 的活化在癌细胞迁移中起着至关重要的作用。因此,它是发现抗癌药物的一个新靶点。在此,我们利用 Schrodinger suit 2021-2 和 GROMACS 2021.6 进行了虚拟筛选和动力学模拟,筛选了大量针对 STK 16 的天然化合物库。结果预测了5种对靶点具有高结合亲和力的分子,其中NPC132329(Arcyriaflavin C)和NPC160898具有更高的结合亲和力和分子力学广义天生表面积(MM/GBSA),表明其优于标准抑制剂。分子动力学(MD)模拟研究表明,与标准药物和选择性 STK 16 抑制剂相比,STK 16-NPC132329 复合物的均方根偏差最小,STK 16-NPC160898 最为稳定。根据均方根波动轨迹,STK 16-NPC132329 和 STK 16-NPC160898 复合物的波动最小,NPC132329 和 NPC160898 分别与靶标结合位点的氨基酸残基形成 2 个和 3 个氢键。总体而言,NPC132329和NPC160898是比标准药物和选择性抑制剂更好的STK 16抑制剂,可进一步研究发现新型抗癌药物。
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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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