"Researchers previously measured how knob molecules bound to holes in a saturated solution," explained Barker, "but we wanted to know how fast the knobs were binding to the holes and the length of time the knob and hole interacted to determine if we could optimize these parameters to inhibit fibrin formation."
The researchers measured the hole binding characteristics of six different knob sequences -- each seven or eight amino acids in length -- to evaluate the impact of additional backbone stabilization and/or different charge distributions. They found that the binding rates improved significantly by adding two amino acids, called proline and phenylalanine, for stabilization and having charged configurations in the sixth and seventh positions in the sequences.
"Investigating these binding events under dynamic conditions provided critical information, but the results didn't really surprise us," noted Barker. "Small peptides in aqueous solutions 'wiggle' a lot, so the more stable the molecules are in their active structural state, the better chance they have of establishing a good knob-hole interaction because they're not changing their shape as much."
Analyzing the structural dynamics of the peptides through simulation indicated that the orientation of the arginine amino acid side chain and backbone stability contributed significantly to functional binding of the knobs and holes.
During their investigation, the researchers also identified a novel knob peptide mimic (GPRPFPAC) that exhibited a binding rate to holes one order of magnitude higher than previously published knob sequences --
|Contact: Abby Vogel|
Georgia Institute of Technology Research News