The Interaction of Borate Ions with Cytochrome c Surface Sites: A Molecular Dynamics Study

• Published in: Biophysical journal 1998-11, Vol.75 (5), p.2461-2468
• Main Authors: Taler, Galia, Navon, Gil, Becker, Oren M.
• Format: Article
• Language: English
• Subjects: Animals; Anions - metabolism; Binding Sites - physiology; Borates - chemistry; Cytochrome c Group - chemistry; Horses; Hydrogen Bonding; Lysine - chemistry; Models, Molecular; Mutation - genetics; Protein Binding; Static Electricity
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(98)77690-8

Ionic interactions of cytochrome c play an important role in the electron transfer process. Molecular dynamics simulations of the binding of borate ion, which serves as a model ion, at three different cytochrome c surface sites are performed. This work is motivated by previous NMR studies of cytochrome c in borate solution, which indicate the existence of two types of binding sites, a slow exchange site and a fast exchange 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/Lys 27 and Lys 55/Lys 73) the ion forms two to three hydrogen bonds to the nearest lysine residue. This binding is transient on the time scale of the simulation, demonstrating the feasibility of fast exchange. At the “tight” binding site (near Lys 13/Lys 86), on the other hand, the ion becomes integrated into the protein hydrogen bond network and remains there for the duration of the simulation (exemplifying slow exchange). Binding simulations of the ion at the “tight” site of H26Q mutant cytochrome c also showed integration of the ion into the protein's hydrogen bond network. However, this integration differs in details from the binding of the ion to the native protein, in agreement with previous NMR observations.