Ghadari Rahim, Mohammadzadeh Yousef
Computational Chemistry Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz , Tabriz, Iran .
Assay Drug Dev Technol. 2018 Jul;16(5):266-277. doi: 10.1089/adt.2017.836.
Computational studies were done on the complexes between some commercially available anticancer drugs and their hypothetic derivatives and the CCR5 protein. At first step, the docking studies were done to obtain the best ligand that can inhibit the CCR5 protein. Based on the binding energy results obtained from the docking studies, 16 complexes were selected. Molecular dynamic studies were carried out on these structures and then molecular mechanics-generalized Born surface area calculations were done to find the binding energies of the ligands to the CCR5 protein. Based on the investigation of the binding modes of the ligands to the CCR5 protein, the TYR and ALA have more tendency to bind to the ligand moieties. By decomposing of the binding energies, it was found that the van der Waals interactions have the most important role in the binding of ligands to the protein in comparison with the electrostatic and hydrogen bonding interactions. The results of the interaction potential surface map analysis showed that the nitrogen and oxygen atoms have a relatively similar role in the binding of ligands to the CCR5 protein structure.
对一些市售抗癌药物及其假想衍生物与CCR5蛋白之间的复合物进行了计算研究。第一步，进行对接研究以获得能够抑制CCR5蛋白的最佳配体。基于对接研究获得的结合能结果，选择了16种复合物。对这些结构进行了分子动力学研究，然后进行分子力学-广义玻恩表面积计算以找到配体与CCR5蛋白的结合能。基于对配体与CCR5蛋白结合模式的研究，发现酪氨酸（TYR）和丙氨酸（ALA）更倾向于与配体部分结合。通过分解结合能发现，与静电和氢键相互作用相比，范德华相互作用在配体与蛋白质的结合中起最重要的作用。相互作用势表面图分析结果表明，氮原子和氧原子在配体与CCR5蛋白结构的结合中具有相对相似的作用。
