The entrance and exit paths of chemicals, called tunnels, to enzymes are hypothesized to be an important selectivity filter for their enzymatic reaction. To identify and investigate tunnels in proteins, we have recently developed a stepwise scheme, titled IterTunnel, which allows for tunnels to be iteratively re-calculated during a steered MD simulation [Paper C]. In comparison with existing methods, the major advantage of our method is that it allows the protein to adapt its conformation to the ligand as the ligand traverses through the protein. Unlike existing methods, our approach is designed to identify tunnels that may open as a result of protein flexibility. In the future, we will systematically investigate how structurally different chemicals use different tunnels, how substrate and product might enter and exit through different pathways and how this influences association and dissociation constants.