Development of a Simple Electron Transfer and Polarization Model and Its Application to Biological Systems

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• 作者：David J. Diller
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2017
• 出版时间：January 10, 2017
• 年：2017
• 卷：13
• 期：1
• 页码：329-339
• 全文大小：451K
• ISSN：1549-9626

文摘

Here we present a new method for point charge calculation which we call Q_ET (charges by electron transfer). The intent of this work is to develop a method that can be useful for studying charge transfer in large biological systems. It is based on the intuitive framework of the Q_EQ method with the key difference being that the Q_ET method tracks all pairwise electron transfers by augmenting the Q_EQ pseudoenergy function with a distance dependent cost function for each electron transfer. This approach solves the key limitation of the Q_EQ method which is its handling of formally charged groups. First, we parametrize the Q_ET method by fitting to electrostatic potentials calculated using ab initio quantum mechanics on over 11,000 small molecules. On an external test set of over 2500 small molecules the Q_ET method achieves a mean absolute error of 1.37 kcal/mol/electron when compared to the ab initio electrostatic potentials. Second, we examine the conformational dependence of the charges on over 2700 tripeptides. With the tripeptide data set, we show that the conformational effects account for approximately 0.4 kcal/mol/electron on the electrostatic potentials. Third, we test the Q_ET method for its ability to reproduce the effects of polarization and electron transfer on 1000 water clusters. For the water clusters, we show that the Q_ET method captures about 50% of the polarization and electron transfer effects. Finally, we examine the effects of electron transfer and polarizability on the electrostatic interaction between p38 and 94 small molecule ligands. When used in conjunction with the Generalized-Born continuum solvent model, polarization and electron transfer with the Q_ET model lead to an average change of 17 kcal/mol on the calculated electrostatic component of ΔG.