Accurate descriptions of molecular recognition and chemical reactions are of extreme importance for the understanding of biological processes. On the one hand, quantum chemical calculations are able, at least in principle, to lead to such accuracy, but due to the formidable scaling behavior with system size (O(N2logN) for conventional Hartree-Fock calculations going up to O(N7) for correlated methods) this can only be done for small molecules using standard methods. On the other hand, molecular mechanics calculations can handle very large biomolecules, but no bond breaking or forming, and therefore no chemical reaction can be described. To combine the advantages of the two methods, mixed quantum mechanical / molecular mechanical (QM/MM) calculations have been proposed. Another possibility to reduce the scaling behavior of quantum chemical calculations are fragment-based methods. Prominent examples are the divide-and-conquer approach of Yang and the adjustable density matrix assembler (ADMA) introduced by Mezey, which is the basis for the project proposed here. In these methods, the large molecule is divided into small fragments and independent quantum chemical calculations are performed on all these fragments. In this way, Hartree-Fock as well as density functional theory (DFT) calculations can be performed even for very large systems. For some time we are working on the optimization of the ADMA approach resulting in a high increase in accuracy by the use of additional parts represented as partial charges and the treatment of the fragment borders by hybrid orbitals. Many molecular properties of very large molecules, like energies, electrostatic potentials, and electron densities, can be calculated with high precision using the combination of these improvements. But for the further expansion of the amount of possible applications, geometry optimization of these large molecules is highly desired. This will be conduced in the project proposed here.
