Shamsara Jamal
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Open Med Chem J. 2016 Feb 2;10:1-6. doi: 10.2174/1874104501610010001. eCollection 2016.
Considering different orientation of hydroxyl and thiol groups of receptor residues such as Thr, Tyr, Ser and Cys is an option available on Glide docking software. This is an attempt that can provide more realistic ligand-receptor interactions. Matrix metalloproteinase 13 (MMP-13) is a suggested target for several diseases including osteoarthritis and cancer. MMP-13 was selected as a receptor with reported flexibility in the active site residues. Four residues in the MMP-13 active site were selected and their hydroxyl groups were made flexible during docking: Tyr(241), Thr(242), Tyr(243) and Thr(244). The ability of retrospective virtual screenings using a rigid receptor for discriminating between actives and decoys were compared to those using receptor with different combination of flexible residues. Statistical analysis of the results and inspecting the binding pose of the ligands suggested that the hydroxyl orientation of Tyr(241), Thr(242), Tyr(243) and Thr(244) (in particular Thr(242) and to a lesser extent Thr(244)) had impacts on the MMP-13 docking results.
考虑受体残基（如苏氨酸、酪氨酸、丝氨酸和半胱氨酸）的羟基和硫醇基团的不同取向是Glide对接软件提供的一种选择。这是一种能够提供更真实的配体-受体相互作用的尝试。基质金属蛋白酶13（MMP-13）是包括骨关节炎和癌症在内的多种疾病的潜在靶点。MMP-13被选为一种在活性位点残基具有报道的灵活性的受体。在MMP-13活性位点选择了四个残基，并在对接过程中使它们的羟基具有灵活性：酪氨酸（241）、苏氨酸（242）、酪氨酸（243）和苏氨酸（244）。将使用刚性受体进行回顾性虚拟筛选以区分活性化合物和诱饵的能力与使用具有不同灵活残基组合的受体的能力进行了比较。对结果的统计分析以及检查配体的结合姿势表明，酪氨酸（241）、苏氨酸（242）、酪氨酸（243）和苏氨酸（244）（特别是苏氨酸（242），苏氨酸（244）的影响较小）的羟基取向对MMP-13对接结果有影响。
