Molecular modelling of ABC transporters: from ATP hydrolysis to substrate transport

Abstract

Despite the great advances that have been made in the past decades in the ABC transporters field, the molecular mechanisms involved in transport across membranes remains largely an enigma. To date, questions regarding the molecular mechanism of transport, nucleotide hydrolysis and inorganic phosphate exit from the binding sites are still unanswered. In this thesis the dynamic behavior of several ABC transporters during the ATP-hydrolytic cycle is investigated using molecular modeling methods. The content of this thesis is compiled in three main scientific publications [1-3], corresponding to sections 3, 4 and 5, respectively. Although these three works are performed in prokaryotic family ABC transporters, it is likely that eukaryotic ones use similar mechanisms for nucleotide hydrolysis, inter-domain communication and allocrite translocation.(...)