Scholarlink

<p>Cyclin-dependent kinase 2 (CDK2) is an important regulatory factor of the G1-S phase transition of the cell cycle, and a promising target for developing therapies to treat colon cancer. In this study, Naringenin and versions of its structure (Poriol, 7-Hydroxyflavanone, and Farrerol) were evaluated for their inhibitory potential using a multi-level in silico approach involving molecular docking, density functional theory (DFT), molecular dynamics (MD) simulation, and MMGBSA binding free energy. Naringenin bound with the most favourable affinity (ΔG_bind = − 43.55&#xa0;kcal/mol) to CDK2, which stabilized binding through important active site residue contacts (LEU83, ILE10, and VAL18). DFT derived reactivity descriptors and electrostatic potential maps identified the carbonyl group as a key site of protein–ligand recognition. After 200&#xa0;ns of MD simulation, Naringenin had a stable structure (i.e., RMSD values), and MMGBSA and residue decomposition analyses of each molecule supported favourable binding space energetically. Overall, our study indicated that Naringenin may be a lead compound in drug development targeting CDK2. However, the anticancer potential and pharmacokinetic properties need to be validated with in vitro and in vivo studies. This study demonstrates a rational basis to move Naringenin-based scaffolds forward in preclinical cancer research by employing computational and translational pharmacology.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Naringenin and its structural analogues inhibit CDK2: a combined MD-MMGBSA and protein–ligand interaction study for colon cancer

  • 期刊论文

  • 发表日期：

    2025年9月18日

查看全文
  • Francis Dhiya,
  • K. S. Sindhu,
  • J. Kavitha,
  • Varughese Jibin,
  • Vincent Maria,
  • T. G. Abi

摘要

Cyclin-dependent kinase 2 (CDK2) is an important regulatory factor of the G1-S phase transition of the cell cycle, and a promising target for developing therapies to treat colon cancer. In this study, Naringenin and versions of its structure (Poriol, 7-Hydroxyflavanone, and Farrerol) were evaluated for their inhibitory potential using a multi-level in silico approach involving molecular docking, density functional theory (DFT), molecular dynamics (MD) simulation, and MMGBSA binding free energy. Naringenin bound with the most favourable affinity (ΔG_bind = − 43.55 kcal/mol) to CDK2, which stabilized binding through important active site residue contacts (LEU83, ILE10, and VAL18). DFT derived reactivity descriptors and electrostatic potential maps identified the carbonyl group as a key site of protein–ligand recognition. After 200 ns of MD simulation, Naringenin had a stable structure (i.e., RMSD values), and MMGBSA and residue decomposition analyses of each molecule supported favourable binding space energetically. Overall, our study indicated that Naringenin may be a lead compound in drug development targeting CDK2. However, the anticancer potential and pharmacokinetic properties need to be validated with in vitro and in vivo studies. This study demonstrates a rational basis to move Naringenin-based scaffolds forward in preclinical cancer research by employing computational and translational pharmacology.