From Left to Right, Top: Hemanth Buchireddy, Zoe Bellows, Alagammai Kaliappan, Jerry Alter
Prediction and Verification of Protein Structures
Three dimensional structures of proteins mediate vital processes and determine critical architectures. Detailed structural determinations of these molecules have not kept pace with discovery of new proteins. Further, methods including X-ray crystallography and NMR have significant limitations with respect to multi-protein complexes. Therefore we are developing methods and strategies for predicting complex protein structures in biologically relevant environments and experimentally verifying the validity of these predictions. On the one hand, we predict structures utilizing a variety of computational approaches. On the other hand, we validate structures using chemical reactivities and chemical-physical properties that depend on the protein's three dimensional structure. Mass spectrometry is used prominently in these validations.
Individual DNA repair proteins and the multi-protein nucleotide excision repair complex are being examined using this approach. (Support: Ohio Supercomputer Resource, WSU and College of Science and Mathematics Research Incentive Fund)
Measurement of Low Level Toxicity in Human Samples
Low levels of chemicals, including formaldehyde and various insecticides pervade modern homes and work places. Though the toxic agents do not bother most people at normal, low concentrations, some individuals have clear adverse reactions. Similarly, troops during the Persian Gulf War were probably exposed to very low levels of chemical warfare agents. Some soldiers reported adverse reactions while most remained unaffected. We have hypothesized that in both cases of exposure, sensitive individuals lack normal levels of detoxifying enzymes. We are testing this hypothesis in two ways. First, normal, chemically-sensitive patients and Persian Gulf War veterans are screened for a cadre of detoxifying enzyme activities. Secondly, we screen for the presence of novel toxin-specific enzyme activities in all individuals.
(Support, Department of Defense)
Current Laboratory Members and Associates:
Jon Nuss (Ph.D. Student)
Deacon Sweeney (Ph.D. Student)
Alagammai Kaliappan (M.S. Student)
Twinkle Christian (M.S. Student)
Zoe Bellows (Laboratory Technician)
V. Suneel Koppuravuri (Laboratory Technician)