Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture force.
The force required to rupture the streptavidin-biotin complex was calculated here by computer simulations. The computed force agrees well with that obtained by recent single molecule atomic force microscope experiments. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, additional water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were observed.
Grubmüller
H
H
Theoretische Biophysik, Institut für Medizinische Optik, Ludwig- Maximilians-Universität München, Germany. Helmut.Grubmueller@ Physik.uni-muenchen.de
Heymann
B
B
Tavan
P
P
D001426:Bacterial Proteins / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008024:Ligands; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D008968:Molecular Conformation; D011487:Protein Conformation; D019809:Streptavidin; D013816:Thermodynamics
D001426:Bacterial Proteins; D008024:Ligands; D001710:Biotin; D019809:Streptavidin