THE INTERACTION OF BORATE IONS WITH CYTOCHROME-C SURFACE SITES - A MOLECULAR-DYNAMICS STUDY

Ionic interactions of cytochrome c play an important role in the elect ron transfer process. Molecular dynamics simulations of the binding of berate ion, which serves as a model ion, at three different cytochrom e c surface sites are performed. This work is motivated by previous NM R studies of cytochrome c in berate solution, which indicate the exist ence of two types of binding sites, a slow exchange site and a fast ex change site. These two types of binding behavior were observed in the dynamic simulations, offering a molecular interpretation of ''loose'' and ''tight'' binding. At the ''loose'' binding sites (near Lys(25)/Ly s(27) and Lys(55)/Lys(73)) the ion forms two to three hydrogen bonds t o the nearest lysine residue. This binding is transient on the time sc ale of the simulation, demonstrating the feasibility of fast exchange. At the ''tight'' binding site (near Lys(13)/Lys(86)), on the other ha nd, the ion becomes integrated into the protein hydrogen bond network and remains there for the duration of the simulation (exemplifying slo w exchange). Binding simulations of the ion at the ''tight'' site of H 26Q mutant cytochrome c also showed integration of the ion into the pr otein's hydrogen bond network. However, this integration differs in de tails from the binding of the ion to the native protein, in agreement with previous NMR observations.