Conformational heterogeneity and low-frequency vibrational modes of proteins.
Molecular dynamics simulation and normal mode analysis are used to calculate the vibrational density of states of dihydrofolate reductase complexed with nicotinamide adenine dinucleotide phosphate at 120 K and the results are compared with the experimental spectrum derived from inelastic neutron scattering. The simulation results indicate that the experimental spectrum arises from an average over proteins trapped in different conformations with structural differences mainly in the loop regions, and that these conformations have significantly different low-frequency (<20 cm(-1)) spectra. Thus, the experimentally measured spectrum is an average over the vibrational modes of different protein conformations and is thus inhomogeneously broadened. The implications of this broadening for future neutron scattering experiments and ligand binding calculations are discussed.
Balog
Erika
E
Institut des Hautes Etudes Scientifiques, 35 route de Chartres, 91440, Bures sur Yvette, France.
Smith
Jeremy C
JC
Perahia
David
D
D003198:Computer Simulation; D006801:Humans; D009249:NADP / Q000378:metabolism*; D033363:Neutron Diffraction; D011487:Protein Conformation; D012542:Scattering, Radiation; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014732:Vibration
D009249:NADP; D013762:Tetrahydrofolate Dehydrogenase