The Ultrafast Laser Resource at the University of Pennsylvania is founding the technoogies for multidimensional infrared spectroscopy in biological and biomedical research including drug design. The components of the laboratory are an integrated multifaceted attack on advancing two dimensional infrared methods. Each TR&D is dynamically evolving at the cutting edge of infrared technology, they are mutually supportive. The utility of 2D IR in biomedical applications is increasing substantially. Just within the last year a protein structure has been determined by 2D IR. TR&D's #1 focuses on phototriggered states, the technology combines optical and infrared methods to obtain 2D IR structural-time dependent information during nonequilibrium dynamical processes. The TR&D #2 concerns dual frequency 2D IR which combines into a two dimensional spectrum the excitation of two modes having widely separated frequencies of proteins and proton channels. TR&D#3 involves a specialization on structure determination, to build on previous studies using 2D IR, by improvements in the methodology that are specifically geared towards the equilibrium dynamics of structures of proteins on time scales that have not been achieved by other structural methods. Six DBF's are included: (1)The M2 proton channel of the Influenza A virus: properties of channel water (W.F. DeGrado, UCSF).(2)The structure and dynamics of amyloid A40 fibrils and their formation kinetics (P. Abelson, Upend) (3) Phototriggering of conformational change (A.B. Smith, Upend)) (4) Pushing the Structural Resolution Limit of Linear and Nonlinear Infrared Spectroscopies (F. Gai, Upend) (5) Radical pair dynamics by optically triggered - IR probe spectroscopy (S. Vinogradov, Upend) (6) Spectroscopy and dynamics of HlV-1 RT/inhibitor complexes probed by 2D IR methods and MD simulations (E. Arnold, Rutgers). The proposal also includes seven Collaborative and Service projects on (1) Nitrile and Azide probes (Brewer) (2) Protonated histidines (Londergan) (3) Amyloid fluorescence (Petersson)(4) Blood coagulation (Knshnaswamy) (5) Kinases models (Sarkar)(6)Amyloid kinetics (Dai) (7) Oxygen microscopy (Vinogradov), The Resource provides training for users, and the work is widely disseminated.
The resource employs driving biomedical projects, collaborative and service projects to explore and advance new methods of structure determination with ultrafast infared pulses which are applied in these research projects to expose mechanisms of action of the influenza A virus and HIV AIDS drugs acting on reverse transcriptase, the folding and misfolding of amyloid proteins and of dysregulaed blood coagulation
| Pazos, Ileana M; Ma, Jianqiang; Mukherjee, Debopreeti et al. (2018) Ultrafast Hydrogen-Bonding Dynamics in Amyloid Fibrils. J Phys Chem B : |
| Hilaire, Mary Rose; Ding, Bei; Mukherjee, Debopreeti et al. (2018) Possible Existence of ?-Sheets in the Amyloid Fibrils Formed by a TTR105-115 Mutant. J Am Chem Soc 140:629-635 |
| Mukherjee, Debopreeti; Ortiz Rodriguez, Lilliana I; Hilaire, Mary Rose et al. (2018) 7-Cyanoindole fluorescence as a local hydration reporter: application to probe the microheterogeneity of nine water-organic binary mixtures. Phys Chem Chem Phys 20:2527-2535 |
| Abaskharon, Rachel M; Brown, Stephen P; Zhang, Wenkai et al. (2017) Isotope-Labeled Aspartate Sidechain as a Non-Perturbing Infrared Probe: Application to Investigate the Dynamics of a Carboxylate Buried Inside a Protein. Chem Phys Lett 683:193-198 |
| Lin, Chun-Wei; Mensa, Bruk; Barniol-Xicota, Marta et al. (2017) Activation pH and Gating Dynamics of Influenza A M2 Proton Channel Revealed by Single-Molecule Spectroscopy. Angew Chem Int Ed Engl 56:5283-5287 |
| Ding, Bei; Mukherjee, Debopreeti; Chen, Jianxin et al. (2017) Do guanidinium and tetrapropylammonium ions specifically interact with aromatic amino acid side chains? Proc Natl Acad Sci U S A 114:1003-1008 |
| Hilaire, Mary Rose; Ahmed, Ismail A; Lin, Chun-Wei et al. (2017) Blue fluorescent amino acid for biological spectroscopy and microscopy. Proc Natl Acad Sci U S A 114:6005-6009 |
| Rodgers, Jeffrey M; Abaskharon, Rachel M; Ding, Bei et al. (2017) Fermi resonance as a means to determine the hydrogen-bonding status of two infrared probes. Phys Chem Chem Phys 19:16144-16150 |
| Hilaire, Mary Rose; Mukherjee, Debopreeti; Troxler, Thomas et al. (2017) Solvent Dependence of Cyanoindole Fluorescence Lifetime. Chem Phys Lett 685:133-138 |
| Ahmed, Ismail A; Gai, Feng (2017) Simple method to introduce an ester infrared probe into proteins. Protein Sci 26:375-381 |
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