Natural Products Research Unit, Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.
Comput Biol Med. 2012 Jan;42(1):106-11. doi: 10.1016/j.compbiomed.2011.10.014. Epub 2011 Nov 12.
The present study reports the development of a template for the active binding site of Cdk5 for structure-based drug design. The developed template of Cdk5 was validated by redocking with ligands I (PBD code 1UNG), II (PBD code 1UNL) and III (PBD code 1UNH). The results demonstrate a good match of the docked and the crystallographic binding orientations with RMSD less than 2.0Å. The validation results show that the constructed Cdk5 template is a good model system for predicting ligand binding orientations and binding affinities. Furthermore, the developed template was applied to predict binding mode and binding affinity of thirty-six known Cdk5 inhibitors. The results showed that the binding energy of almost Cdk5 inhibitors related to their biological evaluation.
本研究报告了一种基于结构的药物设计的 Cdk5 活性结合位点模板的开发。通过与配体 I（PBD 代码 1UNG）、II（PBD 代码 1UNL）和 III（PBD 代码 1UNH）的重新对接，验证了所开发的 Cdk5 模板。结果表明，对接和晶体结合取向具有很好的匹配性，RMSD 小于 2.0Å。验证结果表明，所构建的 Cdk5 模板是预测配体结合取向和结合亲和力的良好模型系统。此外，该模板还应用于预测 36 种已知 Cdk5 抑制剂的结合模式和结合亲和力。结果表明，Cdk5 抑制剂的结合能与其生物学评价相关。
