TY - JOUR T1 - Why is THz Sensitive to Protein Functional States? Oxidation State of Cytochrome C JF - Terahertz Science and Technology Y1 - 2010 A1 - He,Y. A1 - Chen, J.-Y. A1 - Knab, J. R. A1 - Zheng, W. A1 - Markelz, A.G. AB -

We investigate the presence of structural collective motions on a picosecond time scale for the heme protein, cytochrome c, as a function of oxidation and hydration, using terahertz (THz) time-domain spectroscopy and molecular dynamics simulations. Structural collective mode frequencies have been calculated to lie in this frequency range, and the density of states can be considered a measure of flexibility. A dramatic increase in the THz response occurs with oxidation, with the largest increase for lowest hydrations and highest frequencies. For both oxidation states the measured THz response rapidly increases with hydration saturating above ~25% (g H2O/g protein), in contrast to the rapid turn-on in dynamics observed at this hydration level for other proteins. Quasi-harmonic collective vibrational modes and dipole-dipole correlation functions are calculated from the molecular dynamics trajectories. The collective mode density of states alone reproduces the measured hydration dependence providing strong evidence of the existence of these collective motions. The large oxidation dependence is reproduced only by the dipole-dipole correlation function, indicating the contrast arises from diffusive motions consistent with structural changes occurring in the vicinity of a buried internal water molecule.

VL - 3 UR - http://www.tstnetwork.org/10.11906/TST.149-162.2010.12.15/ IS - 4 ER - TY - CHAP T1 - Development of Tagless Biosensors for Detecting the Presence of Pathogens T2 - Terahertz Frequency Detection and Identification of Materials and Objects Y1 - 2007 A1 - Markelz, A. G. A1 - Chen, J.-Y. A1 - Knab, J. R. A1 - He, Y. A1 - Ye, S. JF - Terahertz Frequency Detection and Identification of Materials and Objects PB - Springer CY - Dordrecht, The Netherlands VL - ed X.-C. Zhang, R. E. Miles, H. Eisele and A. Krotkus ER - TY - Generic T1 - Ultrafast Carriers Dynamics in GaSb/Mn Random Alloys T2 - Proceedings of the 28th International Conference on the Physics of Semiconductors Y1 - 2006 A1 - Ye, S. A1 - Knab, J. A1 - Chen, J.-Y. A1 - Wang, S. A1 - Cheon, M. A1 - Luo, H. A1 - Markelz, A. G. JF - Proceedings of the 28th International Conference on the Physics of Semiconductors CY - Vienna Austria ER - TY - Generic T1 - Using terahertz spectroscopy as a protein binding assay T2 - Advanced Biomedical and Clinical Diagnostic Systems IV; Y1 - 2006 A1 - Chen, J.-Y. A1 - Knab, J. R. A1 - Ye, S. A1 - He, Y. A1 - Markelz, A. G. AB -

The vibrational modes corresponding to protein tertiary structural motion lay in the far infrared or terahertz frequency range. These collective large scale motions depend on global structure and thus will necessarily be perturbed by ligand binding events. We discuss the use of terahertz dielectric spectroscopy to measure these vibrational modes and the sensitivity of the technique to changes in protein conformation, oxidation state and environment. A challenge of applying this sensitivity as a spectroscopic assay for ligand binding is the sensitivity of the technique to both bulk water and water bound to the protein. This sensitivity can entirely obscure the signal from the protein or protein-ligand complex itself, thus necessitating sophisticated sample preparation making the technique impractical for industrial applications. We discuss methods to overcome this background and demonstrate how terahertz spectroscopy can be used to quickly assay protein binding for proteomics and pharmaceutical research.

JF - Advanced Biomedical and Clinical Diagnostic Systems IV; CY - San Jose, California, United States VL - Proc SPIE 6080, ER - TY - Generic T1 - Measuring Protein Flexibility with Terahertz Spectroscopy: Basic Research and Applications T2 - Proceedings of the IEEE LEOS Summer Topical Meeting Y1 - 2004 A1 - Markelz, A. G. A1 - Chen, J.-Y. A1 - Knab, J. R. A1 - Maeder, M. JF - Proceedings of the IEEE LEOS Summer Topical Meeting CY - San Diego, CA ER - TY - Generic T1 - Thz Dielectric Response As A Function Of Protein Hydration: Intramolecular Coupling Contribution T2 - Proceedings of SPIE Optics East Y1 - 2004 A1 - Markelz, A. G. A1 - Chen, J.-Y. A1 - Knab, J. R. A1 - Maeder, M. JF - Proceedings of SPIE Optics East CY - Philadelphia, PA ER - TY - Generic T1 - Biosensing with Terahertz Spectroscopy: Ligand Binding Effects T2 - Proceedings of the International Symposium on Spectral Sensing Research Y1 - 2003 A1 - Chen, J.-Y. A1 - Cerne, J. A1 - Markelz, A. G. JF - Proceedings of the International Symposium on Spectral Sensing Research CY - Santa Barbara, CA ER - TY - Generic T1 - Terahertz Biosensors based on Xerogel Substrates T2 - Proceedings of the International Symposium on Spectral Sensing Research Y1 - 2003 A1 - Chen, J.-Y. A1 - Cox, W. A1 - Bright, F. V. A1 - Cerne, J. A1 - Markelz, A. G. JF - Proceedings of the International Symposium on Spectral Sensing Research CY - Santa Barbara, CA ER - TY - Generic T1 - Ultrafast THz spectroscopy of photoactive biomolecules T2 - Ultrafast Phenomena in Semiconductors VII Y1 - 2003 A1 - Chen, J.-Y. A1 - Whitmire, S. E. A1 - Markelz, A. G. A1 - Hillebrecht, J. R. A1 - Birge, R. R. JF - Ultrafast Phenomena in Semiconductors VII CY - San Jose, California ER -