Accurate modeling of cation–π interactions in enzymes: a case study on the CDPCho:phosphocholine cytidylyltransferase complex

Abstract

ABSTRACT:Cation- interactions are functionally relevant, strong secondary interactions that play versatile roles in a variety of chemical and biological systems. Therefore it is very important to be able to describe accurately and reliably these interactions. In this study we propose a methodology for the accurate modelling of cation- interactions in proteins using QM/MM calculations. We developed a methodology for computing the many-body interaction energy terms and tested the effect of various factors on the accuracy of the binding energy. We found that once wellequilibrated structures were reached in the MD simulations, very similar results can be obtained for the various snapshots taken from the trajectory. The calculated interaction energies were only slightly influenced by electrostatic embedding of the point charges in the QM/MM calculations, and by QM/MM geometry optimization. The calculated molecular mechanics interaction energies were off by 50% for cation- interactions. Instead, we suggest the calibration of force fields based on fragment-based QM-calculations on geometries obtained from MD simulations to yield reliable binding energies at reduced computational cost.Dedicated to Professor Magdolna Hargittai on the occasion of her 70th birthday.3

Theoretical study on cation–π interaction in graphene fragments

“…18 Since the discovering of this interaction many theoretical approaches explaining its physical origin have been devised. 19 The interaction of the cation with the large, permanent quadrupole moment of aromatic rings was initially established as the driving force of the cation-π interaction. 20,21,22 Other investigations revealed that repulsion and induction contributions are important too.…”