  The ABC (ATP Binding Cassette) transporter protein superfamily comprises a
large number of ubiquitous and functionally versatile proteins conserved from
archaea to humans. ABC transporters have a key role in many human diseases and
also in the development of multidrug resistance in cancer and in parasites.
Although a dramatic progress has been achieved in ABC protein studies in the
last decades, we are still far from a detailed understanding of their molecular
functions. Several aspects of pharmacological ABC transporter targeting also
remain unclear. Here we summarize the conformational and protonation changes of
ABC transporters and the potential use of this information in pharmacological
design. Network related methods, which recently became useful tools to describe
protein structure and dynamics, have not been applied to study allosteric
coupling in ABC proteins as yet. A detailed description of the strengths and
limitations of these methods is given, and their potential use in describing
ABC transporter dynamics is outlined. Finally, we highlight possible future
aspects of pharmacological utilization of network methods and outline the
future trends of this exciting field.
