A tunable QM/MM approach to chemical reactivity, structure and physico-chemical properties prediction

Abstract

In the last decade combined quantum mechanic/ molecular mechanic (QM/MM) methods have been applied to a large variety of chemical problems. This paper describes a new QM/MM implementation that acts as a flexible computational environment. Specifically, geometry optimizations, frequency calculations and molecular dynamics can be performed on the investigated system that can be split up to three different layers corresponding to different levels of accuracy. Here we report, together with a detailed description of the method and its implementation, some test examples on very different chemical problems, which span the wide and diversified area of chemistry (from ground to excited states topics) and show the flexibility, general applicability and accuracy of the presented hybrid approach. Biochemical, photobiological and supra/super-molecular applications are presented for this purpose: (a) the optimized geometry of a rotaxane is compared with its X-ray structure; (b) the computed absorption spectra of the green fluorescent protein and rhodopsin chromophores in different environments (namely solvent and protein) are compared to the corresponding experimental values and the role of the counter ion and ion pairs in tuning the geometrical and optical properties of charged organic chromophores in polar solvents is explored and discussed; (c) problems and open questions related to the model set-up of a protein are investigated in the framework of the TcPRAC-protein racemase; (d) similarities and differences between the QM and QM/MM reaction path for the HIV1-protease enzymatic mechanism are shown and discussed; (e) the delicate anomeric equilibrium of α- and β − D-glucopyranose in water is investigated via QM/MM optimizations and molecular dynamics to show the reliability of the actual implementation in the simulation of solvation effects and delicate balances. Finally, it will be shown that the current implementation (called COBRAMM: Computations at Bologna Relating Ab-initio and Molecular Mechanics Methods) is more than a simple QM/MM method, but a more general hybrid approach with a modular structure that is able to integrate some specialized programs, which may increase the flexibility/efficiency of QM, MM and QM/MM calculations.