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.
Keywords: ABC transporters, conformational change, protein dynamics, network pharmacology, protein structure networks, protonation.
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Published on: 17 May, 2013
Page: [4155 - 4172]