G. Taler et al., THE INTERACTION OF BORATE IONS WITH CYTOCHROME-C SURFACE SITES - A MOLECULAR-DYNAMICS STUDY, Biophysical journal, 75(5), 1998, pp. 2461-2468
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.