Characterization of cisplatin/membrane interactions by QM/MM energy decomposition analysis

Abstract

We extend for the first time a quantum mechanical energy decomposition analysis scheme based on deformation electron densities to a hybrid electrostatic embedding quantum mechanics/molecular mechanics framework. The implemented approach...

On the Permeation of Polychlorinated Dibenzodioxins and Dibenzofurans through Lipid Membranes: Classical MD and Hybrid QM/MM-EDA Analysis

“…In order to shed more light on the driving forces responsible for the TCDD and TCDF permeation and the slight differences encountered between them, an energy analysis of the intermolecular interactions between these molecules and the DOPC lipids has been performed around the free energy minima. This analysis could be performed by relying on the energy provided by the force field [ 21 ]. However, more accurate conclusions can be extracted if a QM/MM scheme is employed in the calculation and decomposition of the interaction energy, as was recently conducted for the permeation of cisplatin through a DOPC bilayer [ 21 ].…”

“…Due to the biological relevance of phosphatidylcholine lipids, DOPC and DPPC membranes are widely chosen as models in experimental and computational investigations. DOPC was chosen as a lipid unit by our group in previous studies of membrane permeability with very satisfactory results in comparison with the available experimental data [ 21 , 23 ]. The membrane was built with the help of the CHARMM-GUI website [ 24 ].…”

“…Additionally, a second-order perturbation scheme is applied to decompose the polarization energy. The relevant theory related to this scheme can be found elsewhere, both for the QM-EDA [ 36 , 37 ] and the QM/MM-EDA [ 21 , 38 ] schemes. Herein, we will only mention that the total interaction energy of Equation (1) becomes partitioned into electrostatic (elec), Pauli repulsion (Pau), induction (ind), and dispersion (disp) energies.…”

“…On the other hand, a comparison with TCDF will provide valuable information about the role played by the membrane permeability on the relative toxicity of dibenzodioxins and dibenzofurans. In order to attain more insight into the process and understand the differences found between TCDD and TCDF, a hybrid QM/MM energy decomposition analysis (QM/MM-EDA) has been applied at specific regions along the permeation path (free energy minima and maxima) [ 21 ]. This is the first time the permeation of dioxins through biological membranes is studied at a quantum mechanical level.…”

MoBioTools: A toolkit to setup quantum mechanics/molecular mechanics calculations

“…The keywords basis and bsse of the template file provide a further degree of flexibility: within the section basis the user can employ customized basis sets (e.g., different basis sets for different atoms), and the bsse keyword provides a way to subdivide the system into two subsystems to request either a fragment calculation or the computation of a property that involves the two subsystems, such as the interaction energy, for which the basis set superposition error (BSSE) 71,72 needs to be corrected. This procedure has been extensively used for generating input files in the past, 73 and in the following section this approach will be applied to a system of chemical interest.…”