PK(A) CALCULATIONS ALONG A BACTERIORHODOPSIN MOLECULAR-DYNAMICS TRAJECTORY

Electrostatic calculations of pK(a)-values are reported along a 400 ps molecular dynamics trajectory of bacteriorhodopsin. The sensitivity o f calculated pK(a) values to a number of structural factors and factor s related to the modelling of the electrostatics are also studied. The results are very sensitive to the choice of internal dielectric const ant of the protein (in the interval 2-4). Moreover it is important to include internal water; molecules and to average over a long enough po rtion (similar to 100 ps) of an equilibrium molecular dynamics traject ory. The internal waters are necessary to get an ion-counter ion compl ex with the Schiff base and Arg 82 protonated and the aspartic groups (85 and 212) deprotonated, The fluctuations along the MD-trajectory do not change the protonation state of internal residues at neutral pH. However, at other pH values the averaging along a trajectory maybe cru cial to get correct protonation states. A relationship is found betwee n the arginine group 82, the aspartic group 85 and the glutamate group 204. Glu 204 is protonated in the ground state but the pK(a) value de creases towards deprotonation when the chromophore isomerizes into the cis state. (C) 1997 Elsevier Science B.V.