In this award, funded by the Experimental Physical Chemistry Program, Prof. Andrei Tokmakoff of the Chemistry Department of the Massachusetts Institute of Technology and his graduate student colleagues will develop two dimensional infrared (2D IR) spectroscopy of amide and water vibrations, and use these in combination with nanosecond laser temperature-jumps to study protein and peptide conformational variation and dynamics.
Besides the broader scientific impacts of the research being supported, the research students working on these projects will gain experience with advanced laser techniques. Prof. Tokmakoff also maintains a Web site(www.mit.edu/~tokmakof/TDQMS/) through which his most recent quantum mechanics course materials are made available. Additional lecture and laboratory course materials are distributed on the MIT OpenCourseWare Web site(http://ocw.mit.edu/OcwWeb/web/home/home/index.htm/).
Under this grant, the Tokmakoff group at MIT studies the dynamics that determine conformational dynamics of proteins and peptides. We wish to understand these fundamental phenomena in equilibrium systems and in real time during biophysical processes. Our experimental approach involves development of two dimensional infrared (2D IR) spectroscopy and its use in describing transient molecular structure and structural variation. Our experimental work is complemented by theoretical work on nonlinear spectroscopy, statistical mechanical modeling of dynamics and relaxation, and molecular dynamics computer simulations. The results of this project include publications on the following projects: (1) The development of methods for transient nonlinear spectroscopy including transient 2D IR and transient heterodyne-dispersed vibrational echo (HDVE) methods, (2) the 2D IR spectroscopy of insulin dimer formation used to characterize the association and structure of insulin monomers, (3) the conformational variation and folding of β-hairpin peptides such as TrpZip2, (4) the 2D IR spectroscopy of DNA and RNA base vibrations, (5) the conformation of short elastin-like peptides, and (6) the characterization of binding of monovalent cations by antibiotic ionophores with 2D IR. This grant resulted in 9 peer-reviewed publications, and one PhD thesis. The work involved effort from five graduate students, 1 postdoctoral fellow, and 3 undergraduate students. These trainees presented their research in 11 oral presentations and posters at national and international meetings. This work also supported continuing collaborations with Jasper Knoester (University of Groningen), Alipasha Vaziri (University of Vienna), and Kimberly Hamad-Schifferli (MIT).
