title: Vibrational softening of a protein on ligand binding.
abstract: Neutron scattering experiments have demonstrated that binding of the cancer drug methotrexate softens the low-frequency vibrations of its target protein, dihydrofolate reductase (DHFR). Here, this softening is fully reproduced using atomic detail normal-mode analysis. Decomposition of the vibrational density of states demonstrates that the largest contributions arise from structural elements of DHFR critical to stability and function. Mode-projection analysis reveals an increase of the breathing-like character of the affected vibrational modes consistent with the experimentally observed increased adiabatic compressibility of the protein on complexation.
authors.affiliation: Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Balog
authors.forename: David
authors.initials: D
authors.lastname: Perahia
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
authors.forename: Franci
authors.initials: F
authors.lastname: Merzel
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008727:Methotrexate / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009502:Neutrons; D012542:Scattering, Radiation; D013329:Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014732:Vibration
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate