Biology – Quantitative Biology – Biomolecules
Scientific paper
2008-09-03
Biology
Quantitative Biology
Biomolecules
6 pages, 3 figures; to appear in "Proteins: Structure, Function, and Bioinformatics"
Scientific paper
The binding of a ligand molecule to a protein is often accompanied by conformational changes of the protein. A central question is whether the ligand induces the conformational change (induced-fit), or rather selects and stabilizes a complementary conformation from a pre-existing equilibrium of ground and excited states of the protein (selected-fit). We consider here the binding kinetics in a simple four-state model of ligand-protein binding. In this model, the protein has two conformations, which can both bind the ligand. The first conformation is the ground state of the protein when the ligand is off, and the second conformation is the ground state when the ligand is bound. The induced-fit mechanism corresponds to ligand binding in the unbound ground state, and the selected-fit mechanism to ligand binding in the excited state. We find a simple, characteristic difference between the on- and off-rates in the two mechanisms if the conformational relaxation into the ground states is fast. In the case of selected-fit binding, the on-rate depends on the conformational equilibrium constant, while the off-rate is independent. In the case of induced-fit binding, in contrast, the off-rate depends on the conformational equilibrium, while the on-rate is independent. Whether a protein binds a ligand via selected-fit or induced-fit thus may be revealed by mutations far from the protein's binding pocket, or other "perturbations" that only affect the conformational equilibrium. In the case of selected-fit, such mutations will only change the on-rate, and in the case of induced-fit, only the off-rate.
Deuster Carola von
Weikl Thomas R.
No associations
LandOfFree
Selected-fit versus induced-fit protein binding: Kinetic differences and mutational analysis does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.
If you have personal experience with Selected-fit versus induced-fit protein binding: Kinetic differences and mutational analysis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Selected-fit versus induced-fit protein binding: Kinetic differences and mutational analysis will most certainly appreciate the feedback.
Profile ID: LFWR-SCP-O-104881