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The quantum mechanics/molecular mechanics (QM/MM) method is a multi-scale simulation method that is widely used in simulations of realistic materials in which large electronic reorganizations take place (for example enzymatic catalysis, organocatalysis, highly polarized systems). It is particularly suitable when the problem under investigation requires a quantum mechanics treatment of a small region of the system but the environment around the centre can be treated using molecular mechanics. The usage of QM/MM approach requires the knowledge of more features and parametres in the setup than usual simulations. Therefore events where the QM/MM is taught from the basics to applications are very much needed. The goal of the present school is to teach the participants the skills needed to start QM/MM simulations. The emphasis is in biochemical and biological systems, but the same or similar approach can be used in other fields as well.
- Preparation and equilibration of a biochemical system prior to any QM approach and QM/MM partitioning. We will illustrate with specific examples how to prepare the starting system and how to perform a classical molecular dynamics pre-run to bring the system from a “frozen” pristine crystallographic structure to an ambient-temperature equilibrated one.
* The problem of the solvent. Experimental crystallographic data generally provide only the coordinates - with a finite resolution - of the non-hydrogen atoms of either a protein or a nucleic acid and in some cases their counter-ions. At very best, a few water molecules are included (O atoms only) if these did not evaporate during the crystallization phase. We shall discuss how to add the missing hydrogen atoms and how to include the full solvent, an essential element of biochemical systems both in in vivo and in vitro environments.
* We show guidelines about how to select the specific water molecules that (might) undergo chemical reactions and, hence, cannot be treated at a classical level.
* We shall focus on different methods to setup covalent boundaries between the QM and the MM subsystem (link atoms, frontier orbitals, optimized effective core potentials, scaled-position link atom method, etc.), pointing out their advantages and drawbacks.
* Crucial parameters to be selected and controlled by the user before and during the simulation will be discussed in detail.
* Time scale problem of QM/MM simulations, performance and stability of QM/MM dynamical simulations and accuracy of such a description, as well as the arbitrary partitioning of a large complex biological system will be presented.
Funding: partial funding will be provided to all students, except those working in Lausanne