Simulating proton translocations in proteins: Probing proton transfer pathways in the Rhodobacter sphaeroides reaction center

A general method for simulating proton translocations in proteins and for e xploring the role of different proton transfer pathways is developed and ex amined. The method evaluates the rate constants for proton transfer process es using the energetics of the relevant proton configurations. The energies (Delta G((m))) of the different protonation states are evaluated in two st eps. First, the semimicroscopic version of the protein dipole Langevin dipo le (PDLD/S) method is used to evaluate the intrinsic energy of bringing the protons to their protein sites, when the charges of all protein ionized re sidues are set to zero. Second, the interactions between the charged groups are evaluated by using a Coulomb's Law with an effective dielectric consta nt. This approach, which was introduced in an earlier study by one of the a uthors of the current report, allows for a very fast determination of any D elta G((m)) and for practical evaluation of the time-dependent proton popul ation: That is, the rate constants for proton transfer processes are evalua ted by using the corresponding Delta G((m)) values and a Marcus type relati onship, These rate constants are then used to construct a master equation, the integration of which by a fourth-order Runge-Kutta method yields the pr oton population as a function of time. The integration evaluates, 'on the f ly' the changes of the rate constants as a result of the time-dependent cha nges in charge-charge interaction, and this feature benefits from the fast determination of Delta G((m)). The method is demonstrated in a preliminary study of proton translocation processes in the reaction center of Rhodobact er sphaeroides. It is found that proton transfer across water chains involv es significant activation barriers and that ionized protein residues probab ly are involved in the proton transfer pathways. The potential of the prese nt method in analyzing mutation experiments is discussed briefly and illust rated. The present study also examines different views of the nature of pro ton translocations in proteins. It is shown that such processes are control led mainly by the electrostatic interaction between the proton site and its surroundings rather than by the local bond rearrangements of water molecul es that are involved in the proton pathways, Thus, the overall rate of prot on transport frequently is controlled by the highest barrier along the cond uction pathway. Proteins 1999;36:484-500. (C) 1999 Wiley-Liss, Inc.