Effect of quantum mechanical charges in binding sites of metalloproteins

作者：Cho Art E^*

来源：BioChip Journal, 2007, 1(1): 70-75.

• docking
• QM/MM
• charge model
• metalloproteins

Conventional docking methods assume fixed charge model from force field parameters. Combined quantum mechanics/molecular mechanics (QM/MM) method has been applied to docking as a variable charge model and shown to exhibit improvement on the docking accuracy over fixed-charge-based methods. However, there are a number of examples for which adoption of variable charge model fails to reproduce the native binding mode. In particular, the method fails more often for metal-ion-containing proteins, metalloproteins. This class of proteins has highly polarized binding sites at which high-coordinate-numbered metal ions reside. We examine the docking results of this group of proteins and analyze the detailed interactions involved. We deduce the mechanism for success and failure of variable charge model. It is argued that extension of QM/MM docking method would correct the over-fitted charges so as to lead to better docking accuracy for docking of metalloproteins.