DNA replication is at the core of life. Yet, despite pioneering studies, this complex biochemical process is still incompletely understood. One issue is the immensely high fidelity with which DNA replication occurs. In the standard model, this high accuracy was originally entirely ascribed to the specificity of the hydrogen-bonding interactions in the Watson-Crick pairs adenine-thymine (AT) and guanine-cytosine (GC). Meanwhile it is clear that also other factors are decisive, in particular, the steric-shape complementarity of DNA bases in connection with the requirement that the resulting base pair fits, sterically, into the active-site pocket of the DNA polymerase. Other mechanisms that are likely to play a role in this process of biomolecular recognition are solvent effects, π-π stacking interactions, the helical structure of DNA, and many more. This is ongoing work with the potential to uncover ground-breaking insights into the chemical foundations of life.
How Mg2+ Ions Lower the SN2@P Barrier in Enzymatic Triphosphate Hydrolysis
M. A. van Bochove, G. Roos, C. Fonseca Guerra, T. A. Hamlin, F. M. Bickelhaupt
Glucose-Nucleobase Pseudo Base Pairs: Biomolecular Interactions within DNA
E. Vengut-Climent, I. Gomez-Pinto, R. Lucas, P. Penalver, A. Avino, C. Fonseca Guerra, F. M. Bickelhaupt, R. Eritja, C. Gonzalez, J. C. Morales
Selectivity in DNA Replication. Interplay of Steric Shape, Hydrogen Bonds, π-Stacking and Solvent Effects
J. Poater, M. Swart, C. Fonseca Guerra, F. M. Bickelhaupt