Celine Nieuwland from the group of Prof. F. Matthias Bickelhaupt, Prof. Dr. Célia Fonseca Guerra and Dr. Trevor A. Hamlin (VU Amsterdam) will visit the group of Prof. Dr. Marcel Swart at the University of Girona.
DNA replication is at the core of life. Yet, despite revolutionary insights, this complex biochemical process is still not completely understood. One issue is the immensely high fidelity at which DNA replication occurs in the active site of the enzyme DNA polymerase. In the standard model, this high fidelity was originally entirely ascribed to the specificity of the hydrogen-bonding interactions in the Watson–Crick base pairs adenine–thymine (A–T) and guanine–cytosine (G–C). By now, it is clear that also other factors are decisive, such as the steric-shape of DNA bases and their fitting into the active-site pocket of DNA polymerase, but also solvent effects and π– π stacking interactions. Molecular modelling can help elucidate biochemical processes. But since the fidelity of DNA polymerase depends on both electronic and steric effects, it is crucial to simulate the process at the active site at a high computational level, but also include the steric environment resulting from embedding in the active site of the enzyme. In this project, we aim at the development of a QM/MM description for the simulation of the DNA Polymerase/DNA complex in order to understand the process of DNA replication.