Jenwitheesuk Ekachai, Samudrala Ram
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA.
BMC Struct Biol. 2003 Apr 1;3:2. doi: 10.1186/1472-6807-3-2.
The accurate prediction of enzyme-substrate interaction energies is one of the major challenges in computational biology. This study describes the improvement of protein-ligand binding energy prediction by incorporating protein flexibility through the use of molecular dynamics (MD) simulations.
Docking experiments were undertaken using the program AutoDock for twenty-five HIV-1 protease-inhibitor complexes determined by x-ray crystallography. Protein-rigid docking without any dynamics produced a low correlation of 0.38 between the experimental and calculated binding energies. Correlations improved significantly for all time scales of MD simulations of the receptor-ligand complex. The highest correlation coefficient of 0.87 between the experimental and calculated energies was obtained after 0.1 picoseconds of dynamics simulation.
Our results indicate that relaxation of protein complexes by MD simulation is useful and necessary to obtain binding energies that are representative of the experimentally determined values.
准确预测酶 - 底物相互作用能是计算生物学中的主要挑战之一。本研究描述了通过使用分子动力学（MD）模拟纳入蛋白质柔性来改进蛋白质 - 配体结合能预测。
使用AutoDock程序对通过X射线晶体学确定的25种HIV - 1蛋白酶 - 抑制剂复合物进行对接实验。没有任何动力学的蛋白质刚性对接在实验和计算的结合能之间产生了0.38的低相关性。受体 - 配体复合物的MD模拟在所有时间尺度上相关性都有显著提高。在0.1皮秒的动力学模拟后，实验和计算能量之间获得了最高相关系数0.87。
我们的结果表明，通过MD模拟使蛋白质复合物松弛对于获得代表实验确定值的结合能是有用且必要的。
