The non empirical local self consistent field method: Application to quantum mechanics/molecular mechanics (QM/MM) modeling of large biomolecular systems

Abstract

The present chapter starts with an analysis of the problems encountered when applying a mixed Quantum Mechanics/Molecular Mechanics to a large molecular system, which cannot be approached at a full quantum level of computation and a review of the possible solutions. A Non Empirical Local Self Consistent Field methodology, allowing computing at any quantum chemical level a part of a very large molecule interacting with the rest of this molecule is described in some detail. This approach is illustrated by various applications to the spectroscopic properties of various bio-macromolecules. Finally, and as a test case we will focus on the QM/MM modelling of spectroscopic and photophysical properties of exogenous chromophores interacting with DNA. Hence, we will show how the combination of high-level QM/MM methods with Molecular Dynamics simulations allows us to gain unprecedented insights in the process of DNA Photosensitization that is of paramount importance to understand the induction of DNA photolesions and to unravel novel anticancer therapeutic strategies.