02692nas a2200265   4500008004500000020001400045245010200059210006900161260000800230300001400238490000700252520189600259653001402155653002102169653002302190653002802213653003102241653001702272653001002289653002202299100001702321700001902338700002002357856004902377       2020                        Engldsh    a1549-959600aPersistent Protein Motions in a Rugged Energy Landscape Revealed by Normal Mode Ensemble Analysis0 aPersistent Protein Motions in a Rugged Energy Landscape Revealed  cDec  a6419-64260 v603 a<p>Proteins are allosteric machines that couple motions at distinct, often distant, sites to control biological function. Low-frequency structural vibrations are a mechanism of this long-distance connection and are often used computationally to predict correlations, but experimentally identifying the vibrations associated with specific motions has proved challenging. Spectroscopy is an ideal tool to explore these excitations, but measurements have been largely unable to identify important frequency bands. The result is at odds with some previous calculations and raises the question what methods could successfully characterize protein structural vibrations. Here we show the lack of spectral structure arises in part from the variations in protein structure as the protein samples the energy landscape. However, by averaging over the energy landscape as sampled using an aggregate 18.5 mu s of all-atom molecular dynamics simulation of hen egg white lysozyme and normal-mode analyses, we find vibrations with large overlap with functional displacements are surprisingly concentrated in narrow frequency bands. These bands are not apparent in either the ensemble averaged vibrational density of states or isotropic absorption. However, in the case of the ensemble averaged anisotropic absorption, there is persistent spectral structure and overlap between this structure and the functional displacement frequency bands. We systematically lay out heuristics for calculating the spectra robustly, including the need for statistical sampling of the protein and inclusion of adequate water in the spectral calculation. The results show the congested spectrum of these complex molecules obscures important frequency bands associated with function and reveal a method to overcome this congestion by combining structurally sensitive spectroscopy with robust normal mode ensemble analysis.</p>10aChemistry10aComputer Science10amolecular-dynamics10aPharmacology & Pharmacy10aphotoactive yellow protein10aspectroscopy10astate10avibrational-modes1 aRomo, T., D.1 aGrossfield, A.1 aMarkelz, A., G.  uhttps://markelz.physics.buffalo.edu/node/24100492nas a2200145   4500008004100000245008500041210006900126260001200195100001300207700001700220700001300237700001900250700002000269856005700289       2019                        eng d00aProtein Intramolecular Motions with Deuteration and Inhibitor Binding Dependence0 aProtein Intramolecular Motions with Deuteration and Inhibitor Bi  c03/20191 aDeng, Y.1 aMcKinney, J.1 aRomo, T.1 aGrossfield, A.1 aMarkelz, A., G.  uhttps://meetings.aps.org/Meeting/MAR19/Session/R63.3