The specific goals of this project are to (1) develop computational strategies to efficiently predict and simulate proton transfer for amino acids and other bio molecules (2) describe generic mechanisms of proton transfer in proteins, based on simulations of ion pumps and other proton-coupled transmembrane transporters (3) describe the role of protons in the transmembrane transport of other ions, such as Na+ and K+ (4) to delineate the proton transfer pathways which lead to the specific sites that protons bind to in transmembrane transporters, specifically the Na+ K+ ATPase (NKA) and the H+ K+ ATPase (HKA) pumps and (6) to re-interpret crystallography and biochemical data on ion pumps in the light of the new proton transport simulations (protonation states are impossible to predict in crystal structures).The movement of protons within proteins is a key enzymatic process involved in several cellularfunctions such as photosynthesis, electron transport chains in mitochondria, ion pumping andacidification of stomach and cellular compartments to name a few. Computational treatment ofproton movement in proteins has proven refractory because of many factors. In this project, we propose to develop a new hybrid computational method to investigate proton transfer in complex proteins. Such a method will enable researchers to efficiently explore proton transfer in a large variety of biological complexes, as well as in non-biological systems such as fuel cell polymer membranes.The project will unravel the molecular mechanism of action of ion transporters, and other proteins involved in proton-coupled reactions or transport. We will obtain both “molecular movies” of ion and proton transport, and quantitative thermodynamics descriptions of the ion and/or substrate transport process.The project will constantly interface with state-of-the-art experimental measurements in the laboratories of collaborators. We will work together with experts in Finland, Aarhus and SDU.
|Effective start/end date||01/05/2015 → 31/10/2017|