Proton Transfer on the Molecular Surface of Proteins and Model Systems

Abstract

AbstractProton transfer (PT) reactions take place on the molecular surface of proteins, membranes, ionic polymers, and other molecules. The rates of the reactions can be followed experimentally, while the atomistic details can be elucidated by molecular modeling. This manuscript gives a brief overview of the use of computer simulations and molecular modeling, in conjuction with experiments, to study PT reactions on the surface of solvated molecules. An integrative approach is discussed, where molecular dynamics simulations are performed with a protein, and quantum‐mechanics‐based calculations are performed on a small molecule. The simulation results allow the identification of the necessary conditions that yield PT reactions on the molecular surface. The reactions are efficient when they involve a donor and acceptor located a few Å apart and under the influence of a negative electrostatic field. In proton‐pumping proteins, it is possible to identify such conditions a priori and locate proton‐attracting antenna domains without the need to mutate each potential donor and acceptor. Based on density functional theory calculations, the arrangement of water molecules that interconnect the donor and acceptor moieties is suggested as the rate‐limiting step for proton transfer on the molecular surface.