Computational analysis of bevacizumab binding with protein receptors for its potential anticancer activity.

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nada Alsakhen, Enas S Radwan, Imran Zafer, Husam Abed Alfattah, Israa M Shamkh, Md Tabish Rehman, Moayad Shahwan, Khalid Ali Khan, Shimaa A Ahmed
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引用次数: 0

Abstract

Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. In this study, we investigated the binding free energy (ΔG) of bevacizumab, an anti-cancer therapy targeting angiogenesis through the inhibition of vascular endothelial growth factor (VEGF), with various proto-oncogenes including CDK4, EGFR, frizzled, IGFR, OmoMYC, and KIT. Our in-silico investigation revealed that hydrogen bonding is pivotal in inducing conformational changes within the DNA structure, impeding its replication and preventing cell death. Molecular docking results revealed the presence of crucial hydrogen bonds and supported the formation of stable bevacizumab complexes. The molecular docking scores for the tested complexes were CDK4 (Score = -7.2 kcal/mol), EGFR (Score = -8.5 kcal/mol), frizzled (Score = -6.9 kcal/mol), IGFR (Score = -7.8 kcal/mol), KIT (Score = -6.5 kcal/mol), and MYC (Score = -8.3 kcal/mol). The binding mode demonstrated vital hydrogen bonds correlated with the observed energy gap. Notably, the calculated binding free energies of the tested compounds are as follows: CDK4 (ΔG = 24275.195 ± 6411.293 kJ/mol), EGFR (ΔG = 363273.625 ± 8731.466 kJ/mol), frizzled (ΔG = 181751.990 ± 28438.515 kJ/mol), IGFR (ΔG = 162414.725 ± 10728.367 kJ/mol), KIT (ΔG = 40162.585 ± 4331.017 kJ/mol), and MYC (ΔG = 434783.463 ± 53989.676 kJ/mol). Furthermore, through extensive 100 ns MD simulations, we observed the formation of a stable bevacizumab complex structure. The simulations confirmed the stability of the bevacizumab complex with the proto-oncogenes. The results of this study highlight the potential of bevacizumab complex as a promising candidate for anticancer treatment. The identification of hydrogen bonding, along with the calculated binding free energies and molecular docking scores, provides valuable insights into the molecular interactions and stability of the bevacizumab complexes. These findings and the extensive MD simulations open new avenues for future research and development of bevacizumab as a targeted therapy for breast cancer and other related malignancies.

贝伐珠单抗与蛋白受体结合的计算分析,以了解其潜在的抗癌活性。
乳腺癌是一项重大的全球性挑战,促使研究人员探索新的潜在治疗方法。贝伐珠单抗是一种通过抑制血管内皮生长因子(VEGF)针对血管生成的抗癌疗法,在本研究中,我们研究了贝伐珠单抗与多种原癌基因(包括 CDK4、表皮生长因子受体、凋亡因子、IGFR、OmoMYC 和 KIT)的结合自由能(ΔG)。我们的室内研究发现,氢键在诱导 DNA 结构构象变化、阻碍其复制和防止细胞死亡方面起着关键作用。分子对接结果显示存在关键的氢键,并支持形成稳定的贝伐珠单抗复合物。受测复合物的分子对接得分分别为 CDK4(得分=-7.2 kcal/mol)、表皮生长因子受体(得分=-8.5 kcal/mol)、凋亡因子(得分=-6.9 kcal/mol)、表皮生长因子受体(得分=-7.8 kcal/mol)、KIT(得分=-6.5 kcal/mol)和 MYC(得分=-8.3 kcal/mol)。所显示的重要氢键结合模式与观察到的能隙相关。值得注意的是,测试化合物的计算结合自由能如下:CDK4(ΔG = 24275.195 ± 6411.293 kJ/mol)、表皮生长因子受体(ΔG = 363273.625 ± 8731.466 kJ/mol)、皱纹(ΔG = 181751.990 ± 28438.515 kJ/mol)、IGFR(ΔG = 162414.725 ± 10728.367 kJ/mol)、KIT(ΔG = 40162.585 ± 4331.017 kJ/mol)和 MYC(ΔG = 434783.463 ± 53989.676 kJ/mol)。此外,通过大量的 100 ns MD 模拟,我们观察到形成了稳定的贝伐珠单抗复合物结构。模拟证实了贝伐珠单抗与原癌基因复合物的稳定性。这项研究的结果凸显了贝伐珠单抗复合物作为抗癌治疗候选药物的潜力。氢键的识别以及计算出的结合自由能和分子对接得分,为了解贝伐珠单抗复合物的分子相互作用和稳定性提供了宝贵的见解。这些发现和大量的 MD 模拟为贝伐珠单抗作为乳腺癌和其他相关恶性肿瘤靶向疗法的未来研究和开发开辟了新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Biomolecular Structure & Dynamics
Journal of Biomolecular Structure & Dynamics 生物-生化与分子生物学
CiteScore
8.90
自引率
9.10%
发文量
597
审稿时长
2 months
期刊介绍: The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.
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