iMOS Master: On the Mechanism of ATP Hydrolysis in…

On the Mechanism of ATP Hydrolysis in ABC Transporter TAP, 2015

Hendrik Göddeke

Adenosine triphosphate (ATP) is the energy currency molecule in the cell, and its hydrolysis is one of the most fundamental chemical reactions in biological systems. One example of a protein family that requires ATP binding and hydrolysis for function are the ATP-binding cassette transporters (TAP). In order to study the ATP hydrolysis inside TAP, a hybrid quantum mechanics / molecular mechanics (QM/MM) approach was used to describe the hydrolysis reaction by means of density functional theory (DFT) and the rest of the system by means of a classical force field.

Hendrik-Diagram from m.thesis_1340x768

Potential of Mean Force (PMF) along the associative reaction coordinate.

All examined mechanisms (associative, dissociative, concerted, glutamate-catalyzed and histidine-catalyzed) failed to capture the exothermicity of ATP hydrolysis, in line with previous QM/MM studies. Due to computational costs, only one water molecule was included in the QM subsystem for the nucleophilic attack, excluding a possible mechanism involving proton wires with several waters. Therefore, including more water molecules in the QM subsystem could provide a more realistic picture and hence, could help in understanding the power stroke of ABC transporters.

Link to  Master course in Molecular Sciences and Simulation (iMOS) at Ruhr-University Bochum


About the Author

Henfrik GoddekeHendrik Göddeke was born in Meschede and holds a BSc in Molecular Biology with a focus on Bioinformatics from Westphalian University Gelsenkirchen. He then moved to Bochum for iMOS. The international course was carried out in the Tobias lab at UC Irvine. He finished iMOS in September 2015 and is now doing his PhD in the Schäfer group.