title: Moving in the Right Direction: Protein Vibrations Steering Function.
abstract: Nearly all protein functions require structural change, such as enzymes clamping onto substrates, and ion channels opening and closing. These motions are a target for possible new therapies; however, the control mechanisms are under debate. Calculations have indicated protein vibrations enable structural change. However, previous measurements found these vibrations only weakly depend on the functional state. By using the novel technique of anisotropic terahertz microscopy, we find that there is a dramatic change to the vibrational directionality with inhibitor binding to lysozyme, whereas the vibrational energy distribution, as measured by neutron inelastic scattering, is only slightly altered. The anisotropic terahertz measurements provide unique access to the directionality of the intramolecular vibrations, and immediately resolve the inconsistency between calculations and previous measurements, which were only sensitive to the energy distribution. The biological importance of the vibrational directions versus the energy distribution is revealed by our calculations comparing wild-type lysozyme with a higher catalytic rate double deletion mutant. The vibrational energy distribution is identical, but the more efficient mutant shows an obvious reorientation of motions. These results show that it is essential to characterize the directionality of motion to understand and control protein dynamics to optimize or inhibit function.
authors.affiliation: Department of Physics, University at Buffalo, State University of New York, Buffalo, New York. Electronic address: kniessen@buffalo.edu.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Niessen
authors.affiliation: Department of Physics, University at Buffalo, State University of New York, Buffalo, New York.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Dipartimento di Fisica e Geologia, Università di Perugia, Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paciaroni
authors.affiliation: Dipartimento di Fisica e Geologia, Università di Perugia, Perugia, Italy; CNR-IOM c/o Dipartimento di Fisica e Geologia, Università di Perugia, Perugia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Orecchini
authors.affiliation: Hauptman-Woodward Medical Research Institute and Department of Structural Biology, University at Buffalo, State University of New York, Buffalo, New York.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Snell
authors.affiliation: Department of Physics, University at Buffalo, State University of New York, Buffalo, New York; Hauptman-Woodward Medical Research Institute and Department of Structural Biology, University at Buffalo, State University of New York, Buffalo, New York. Electronic address: amarkelz@buffalo.edu.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Markelz
mesh_terms: D019277:Entropy; D056004:Molecular Dynamics Simulation; D009068:Movement; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D014732:Vibration
chemical_list: D009113:Muramidase