Protein-carbohydrate and protein-protein interactions: using models to better understand and predict specific molecular recognition
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The function of the Department of Chemical and Biological Engineering has been to prepare students for the study and application of chemistry in industry. This focus has included preparation for employment in various industries as well as the development, design, and operation of equipment and processes within industry.Through the CBE Department, Iowa State University is nationally recognized for its initiatives in bioinformatics, biomaterials, bioproducts, metabolic/tissue engineering, multiphase computational fluid dynamics, advanced polymeric materials and nanostructured materials.
History
The Department of Chemical Engineering was founded in 1913 under the Department of Physics and Illuminating Engineering. From 1915 to 1931 it was jointly administered by the Divisions of Industrial Science and Engineering, and from 1931 onward it has been under the Division/College of Engineering. In 1928 it merged with Mining Engineering, and from 1973–1979 it merged with Nuclear Engineering. It became Chemical and Biological Engineering in 2005.
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1913 - present
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- Department of Chemical Engineering (1913–1928)
- Department of Chemical and Mining Engineering (1928–1957)
- Department of Chemical Engineering (1957–1973, 1979–2005)
- Department of Chemical and Biological Engineering (2005–present)
- College of Engineering(parent college)
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Abstract
Any molecular recognition event results in a change in the free energy of the system. The extent of this change is related to the association constant, such that the more negative the free energy change is, the tighter the interaction between receptor and ligand. Protein-carbohydrate interactions play a critical role in signal transduction, innate immunity, and metabolism. Modeling these interactions is somewhat complicated by the inherent flexibility of carbohydrates as well as their relatively large number of functional groups. An empirical scoring function for docking carbohydrates to proteins, specifically tailored to predict both the correct binding orientation and free energy of binding of the carbohydrate-ligand/protein-receptor complex, will be presented. This new scoring function can predict free energies of binding to within 1.1 kcal/mol residual standard error, a definite improvement over existing scoring functions that result in standard errors well over 2 kcal/mol. Application of automated docking methodology to determine carbohydrate recognition specificity of the C-type lectin, human surfactant protein D, will also be presented. In the second part of the thesis, the role of pi-stacking interactions (e.g. between Tyr side chains) in stabilizing protein folds will be discussed. A 17-residue peptide derived from the naturally occurring anti-microbial peptide tachyplesin I was investigated using NMR spectroscopy. NOE cross-peaks were observed, confirming the existence of this interaction in solution. In the final part of the thesis, a quantitative NMR investigation into the self-association behavior of the regulatory domains of several Tec family member kinases will be presented. Of particular interest, self-association within Bruton's tyrosine kinase (Btk) regulatory domains occurs through the formation of an asymmetric homodimer. Together this work demonstrates the importance of rigorous biophysical characterization of biomolecular recognition events and the interdependence of computational modeling and experimentation.