Proton transfer is involved in a multitude of biochemical processes, such as titration of ionizable residues in proteins, enzyme catalysis, proton channels, proton pumps, secondary transporters, and proton-powered motors, such as ATP synthase. Many of these processes take place due to the storage of energy in electrochemical proton gradients across biological membranes. The theoretical study of these processes is hampered by the inability of classical molecular dynamics simulations to accommodate proton transfer. As a result, investigators have had to rely on much more expensive semi-classical or quantum chemical methods.
A few years back we implemented into the program CHARMM an algorithm that allows proton movement between hydrogen-bonded partners at low computational cost. It is based on periodic attempts to move a proton along H-bonded molecules from eligible donors to eligible acceptors. Acceptance is dependent on the energy change upon instantaneous proton hop [1].
This algorithm was recently applied to the influenza proton channel M2 [2], which is embedded into the viral envelope and allows acidification of the virion when the external pH is lowered. The simulations provided insights into the reasons that this channel allows only inward proton movement.
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