Importance of Protein Vibration Directionality on Function

Abstract

Global protein vibrations have long been associated with protein functionality. Long-range intramolecular vibrations have been measured in proteins using anisotropic absorption in the terahertz frequency range [1,2]. These measurements directly correspond to the directionality of vibrations and show large changes in the directionality of the vibrational displacements for free chicken egg white lysozyme (CEWL) and inhibitor bound CEWL. Normal mode ensemble analysis (NMEA) and quasiharmonic analysis (QHA) calculations of the free and tri-acetylglucosamine (3NAG) bound CEWL dynamics were performed and also show large changes in vibration directionality with binding. This in spite of the calculated energy distribution showing very little change, in agreement with neutron scattering measurements. We investigate the importance of the protein directionality by extending the calculations to a double deletion mutant (DD CEWL) with an activity rate 1.4 times that of WT [3]. The deletions are far from the active site, indicating that the increased activity arises from changes in the dynamics. The calculated anisotropic spectra show large changes with mutation, whereas the energy distribution show practically no change from the WT. Similarities in the bound WT, free DD, and bound DD CEWL NMEA spectra indicate the mutation may be changing the directionality of the vibrations toward more efficient motions. Projections of the low frequency vibrations, from QHA, on the functional displacement show higher overlap of residues around Glu35 and Asp52 in the mutant system. These residues are known to be critical in CEWL functionality. The results reveal that the mutation may be steering the protein toward more functional dynamics without significantly affecting the energy distribution. [1] K.A. Niessen, et al. (2015) DOI: 10.1007/s12551-015-0168-4[2] G. Acbas, et al. (2014) DOI: 10.1038/ncomms4076[3] S. Mine, et al. (1999) DOI: 10.1006/jmbi.1999.2572. Supported by NSF (DBI 1556359, MCB 1616529) and DOE (DE-SC0016317).