Söderhjelm Pär, Aquilante Francesco, Ryde Ulf
Department of Theoretical Chemistry, Lund University, Chemical Center, SE-22100 Lund, Sweden.
J Phys Chem B. 2009 Aug 13;113(32):11085-94. doi: 10.1021/jp810551h.
We have developed a method to estimate accurate interaction energies between a full protein and a bound ligand. It is based on the recently proposed PMISP (polarizable multipole interaction with supermolecular pairs) method (Soderhjelm, P.; Ryde, U. J. Phys. Chem. A 2009, 113, 617), which treats electrostatic interaction by multipoles up to quadrupoles, induction by anisotropic polarizabilities, and nonclassical interactions by explicit quantum mechanical (QM) calculations, using a fragmentation approach. For a whole protein, electrostatics and induction are treated the same way, but for the nonclassical interactions, a Lennard-Jones term from a standard molecular mechanics (MM) force field (e.g., Amber) is used outside a certain distance from the ligand (4-7 A). This QM/MM variant of the PMISP method is carefully tested by varying this distance. Several approximations related to the classical interactions are also evaluated. It is found that one can speed up the calculation by using density functional theory to compute multipoles and polarizabilities but that a proper treatment of polarization is important. As a demonstration of the method, the interaction energies of two ligands bound to avidin are calculated at the MP2/aug-cc-pVTZ level, with an expected relative error of 1-2%.
我们已经开发出一种方法来估算完整蛋白质与结合配体之间的精确相互作用能。该方法基于最近提出的PMISP（与超分子对的可极化多极相互作用）方法（索德赫耶尔姆，P.；赖德，U.《物理化学杂志A》2009年，113卷，617页），该方法通过高达四极的多极来处理静电相互作用，通过各向异性极化率来处理诱导作用，并使用碎片化方法通过显式量子力学（QM）计算来处理非经典相互作用。对于整个蛋白质，静电和诱导作用的处理方式相同，但对于非经典相互作用，在距配体一定距离（4 - 7埃）之外使用标准分子力学（MM）力场（例如安伯力场）中的 Lennard-Jones 项。通过改变这个距离对 PMISP 方法的这种 QM/MM 变体进行了仔细测试。还评估了与经典相互作用相关的几种近似方法。结果发现，使用密度泛函理论来计算多极和极化率可以加快计算速度，但正确处理极化很重要。作为该方法的一个示例，在 MP2/aug-cc-pVTZ 水平上计算了与抗生物素蛋白结合的两种配体的相互作用能，预期相对误差为1 - 2%。
