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.
Balog
Erika
E
IWR, Universität Heidelberg, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany.
Becker
Torsten
T
Oettl
Martin
M
Lechner
Ruep
R
Daniel
Roy
R
Finney
John
J
Smith
Jeremy C
JC
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