Reliable treatment of electrostatics in combined QM/MM simulation of macromolecules

被引:115
作者
Schaefer, P
Riccardi, D
Cui, Q
机构
[1] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA
[2] Univ Wisconsin, Inst Theoret Chem, Madison, WI 53706 USA
基金
美国国家科学基金会;
关键词
D O I
10.1063/1.1940047
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
A robust approach for dealing with electrostatic interactions for spherical boundary conditions has been implemented in the QM/MM framework. The development was based on the generalized solvent boundary potential (GSBP) method proposed by Im [J. Chem. Phys. 114, 2924 (2001)], and the specific implementation was applied to the self-consistent-charge density-functional tight-binding approach as the quantum mechanics (QM) level, although extension to other QM methods is straightforward. Compared to the popular stochastic boundary-condition scheme, the new protocol offers a balanced treatment between quantum mechanics/molecular mechanics (QM/MM) and MM/MM interactions; it also includes the effect of the bulk solvent and macromolecule atoms outside of the microscopic region at the Poisson-Boltzmann level. The new method was illustrated with application to the enzyme human carbonic anhydrase II and compared to stochastic boundary-condition simulations using different electrostatic treatments. The GSBP-based QM/MM simulations were most consistent with available experimental data, while conventional stochastic boundary simulations yielded various artifacts depending on different electrostatic models. The results highlight the importance of carefully treating electrostatics in QM/MM simulations of biomolecules and suggest that the commonly used truncation schemes should be avoided in QM/MM simulations, especially in simulations that involve extensive conformational samplings. The development of the GSBP-based QM/MM protocol has opened up the exciting possibility of studying chemical events in very complex biomolecular systems in a multiscale framework. (c) 2005 American Institute of Physics.
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页数:14
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