Reactions in complex biologically relevant systems: challenges for computational approaches

The ever increasing power of computational architectures allows to investigate reactive phenomena in complex biomolecular systems and environments. Results from such calculations can be compared with experiment and give important insight into microscopic aspects of chemical reactions. We discuss two examples of biologically relevant reaction mechanisms: double proton transfer in a DNA-base pair analogue for which detailed experimental information is available and ligand (re)binding in myoglobin (Mb). For the double proton transfer in the DNA-base pair analogue ab initio molecular dynamics simulations provide direct information on the infrared spectrum that has also been observed experimentally. In the case of ligand rebinding in MbNO, we discuss results from reactive molecular dynamics simulations to investigate the rebinding probability after photodissociation of the NO from myoglobin and compare the findings with experiment. Both reaction types pose different challenges and we highlight and address the computational difficulties in each case. In particular, we explore and discuss the possibilities and limitations of current computational methods to understand reactive processes in systems where several degrees of freedom are important.