Direct determination of vibrational density of states change on ligand binding to a protein.
The change in the vibrational density of states of a protein (dihydrofolate reductase) on binding a ligand (methotrexate) is determined using inelastic neutron scattering. The vibrations of the complex soften significantly relative to the unbound protein. The resulting free-energy change, which is directly determined by the density of states change, is found to contribute significantly to the binding equilibrium.
IWR, Universität Heidelberg, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany.
Erika
E
Balog
Torsten
T
Becker
Martin
M
Oettl
Ruep
R
Lechner
Roy
R
Daniel
John
J
Finney
Jeremy C
JC
Smith
D017666:Deuterium Oxide / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008727:Methotrexate / Q000737:chemistry*; D015233:Models, Statistical; D009249:NADP / Q000737:chemistry; D009502:Neutrons; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D012542:Scattering, Radiation; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*; D013816:Thermodynamics
D008024:Ligands; D011506:Proteins; D009249:NADP; D013762:Tetrahydrofolate Dehydrogenase; D017666:Deuterium Oxide; D008727:Methotrexate