Department of Chemistry, Clemson University, Clemson, South Carolina 29634, USA.
Proteins. 2010 May 15;78(7):1613-7. doi: 10.1002/prot.22691.
The present study addresses the effect of structural distortion, caused by protein modeling errors, on calculated binding affinities toward small molecules. The binding affinities to a total of 300 distorted structures based on five different protein-ligand complexes were evaluated to establish a broadly applicable relationship between errors in protein structure and errors in calculated binding affinities. Relatively accurate protein models (less than 2 A RMSD within the binding site) demonstrate a 14.78 (+/-7.5)% deviation in binding affinity from that calculated by using the corresponding crystal structure. For structures of 2-3 A, 3-4 A, and >4 A RMSD within the binding site, the error in calculated binding affinity increases to 20.8 (+/-5.98), 22.79 (+/-11.3), and 29.43 (+/-11.47)%, respectively. The results described here may be used in combination with other tools to evaluate the utility of modeled protein structures for drug development or other ligand-binding studies.
本研究探讨了由蛋白质建模误差引起的结构扭曲对小分子结合亲和力计算的影响。评估了总共 300 个基于 5 种不同蛋白-配体复合物的扭曲结构，以建立蛋白质结构误差与计算结合亲和力误差之间的广泛适用关系。相对准确的蛋白质模型（结合部位内 RMSD 小于 2 A）与使用相应晶体结构计算的结合亲和力偏差为 14.78（+/-7.5）%。对于结合部位内 RMSD 为 2-3 A、3-4 A 和>4 A 的结构，计算结合亲和力的误差分别增加到 20.8（+/-5.98）%、22.79（+/-11.3）%和 29.43（+/-11.47）%。这里描述的结果可以与其他工具结合使用，以评估建模蛋白结构在药物开发或其他配体结合研究中的效用。
