Weis Aaron, Katebzadeh Kambiz, Söderhjelm Pär, Nilsson Ingemar, Ryde Ulf
Department of Theoretical Chemistry, Lund University, Chemical Centre, P.O. Box 124, SE-221 00 Lund, Sweden.
J Med Chem. 2006 Nov 2;49(22):6596-606. doi: 10.1021/jm0608210.
The free energy of binding between avidin and seven biotin analogues has been calculated with the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method. We have studied how the force field and the method to generate geometries affect the calculated binding free energies. Four different force fields were compared, but we saw no significant difference in the results. However, mixing the force fields used for the geometry generation and energy calculations is not recommended. In the molecular dynamics simulations, explicit water molecules must be used, but the size of the simulated system and the boundary conditions are less important. In fact, nonperiodic simulations with a fixed protein outside a relatively small simulated system (18 A) seem to be a proper approach. The mean absolute error was 9-19 kJ/mol, with a standard error of 5-15 kJ/mol, which arises mainly from the entropy term.
已使用分子力学泊松-玻尔兹曼表面积（MM/PBSA）方法计算了抗生物素蛋白与七种生物素类似物之间的结合自由能。我们研究了力场和生成几何结构的方法如何影响计算出的结合自由能。比较了四种不同的力场，但我们在结果中未发现显著差异。然而，不建议混合用于几何结构生成和能量计算的力场。在分子动力学模拟中，必须使用显式水分子，但模拟系统的大小和边界条件不太重要。实际上，在相对较小的模拟系统（18埃）之外对固定蛋白质进行非周期性模拟似乎是一种合适的方法。平均绝对误差为9 - 19 kJ/mol，标准误差为5 - 15 kJ/mol，这主要源于熵项。
