ABC transporters are modular proteins that use ATP hydrolysis as a power source to pump a broad range of substrates across membranes. They play critical roles in all forms of life and in humans are primarily known for their role in cystic fibrosis and multidrug resistance in cancer therapy. Computationally, the problem is how to study the mechanism of proteins that in their mechanism combine nanosecond events with millisecond or slower functional motions. We are using a combination of quantum calculations, molecular dynamics, normal mode analysis and homology modeling to understand the modes of action of a number of ABC transporters. An approach which combines normal modes and perturbed normal modes as biasing potential in molecular dynamics to investigate the response of transmembrane domains to motions in the ATP-binding domains seems of particular interest at the moment.