MoLife Research Seminar: Prof. Dr. Lars Schaefer
Talk by:
Prof. Dr. Lars Schäfer, Lehrstuhl für Theoretische Chemie, Ruhr-Universität Bochum, D-44780 Bochum - http://www.theochem.ruhr-uni-bochum.de/research/schaefer/
Title:
Working Cycle of an ABC Transporter at the Atomic Level: Conformational Coupling and ATP Hydrolysis in BtuCD-F
ATB-binding cassette (ABC) transporters are molecular machines that are driven by the chemo-mechanical coupling of ATP binding and hydrolysis in the nucleotide-binding domains (NBDs) to conformational changes in the transmembrane domains (TMDs), which ultimately leads to the translocation of substrates across biological membranes. We use molecular dynamics (MD) simulations to investigate the mechanisms underlying the functional working cycle of the type II importer BtuCD-F as a prototypical ABC transporter. Based on multi-microsecond classical force field simulations (long-ranged conformational coupling between NBDs and TMDs) and hybdrid QM/MM free energy simulations (ATP hydrolysis), we obtain an atomic-level picture of the functional working cycle. Our simulations not only agree with -- and provide a detailed interpretation of -- the available experimental data, they also lead to new, experimental testable predictions.