Quantum Mechanics/Classical Mechanics Modeling of Biological Systems

Abstract

The objective of the project was to give an overview and hands-on insight into modern biotechnological modeling in and across several scales (and dimensions), from Quantum Mechanics to Classical Mechanics, from Molecular Mechanics to Molecular Dynamics, and from Single Molecules to Biological Systems. Here we give a starting tour of using the classical Molecular Dynamics software package AMBER [1], and the quantum mechanical Car-Parrinello package CPMD ( www. cpmd.org ) [2]. Introductions to some useful visualization software software specialised for biological systems was also given (Visual Molecular Dynamics) [3]. The main focus of this project is to apply multi-scale, here the so-called QM/MM molecular dynamics, methods to a biological system. In current biophysical modeling two main branches exist; classical force-field MD and static QM calculations. Though both methods are regularly and successfully applied to biological systems, many intrinsic restrictions exist, some of which are greatly reduced or solved by using multi-scale QM/MM MD. In classical MD, the by-far most common approach, the potential energy surface is parametrized through a fitting to empirical and/or theoretical data. They are therefore intrinsically restricted to situations where no significant changes of the electronic structure occur, but for example chemical reactions can only be treated adequately by a quantum mechanical description. Further restrictions include that the force field parameters are pre-defined and do not change when the system changes, either from conformational changes or from changes in the local environment. Secondly, if one wishes to model e.g. metallic centers or more uncommon organic molecules, no parameters may be available and a sometimes arduous and non-trivial parametrization is necessary.