Martin A. Case

Martin A. Case, Ph.D., Research Assistant Professor of Chemistry

Area of expertise

organic chemistry, bioinorganic chemistry, combinatorial chemistry, protein design

Contact Information


Phone: (802) 656-8246

Office: Cook Rm A321



Broadly, our research goals are to elucidate the roles of amino acid side-chain packing in protein folding and stability using dynamic combinatorial libraries.

As a starting point, we are synthesizing proteins of optimal stability. Our design strategy uses a directed self-assembly approach. Peptide modules designed to adopt context-dependent secondary structure are allowed to associate to create higher order topologies. These topologies are defined by the covalent incorporation of metal ion-binding ligands into the peptide modules: the coordination requirements of the metal ions thus direct the ensemble number and orientation.

Kinetically labile metal/ligand systems allow participating modules to exchange under thermodynamic control. The resulting equilibrium population of metal-assembled proteins constitutes a dynamic combinatorial library, which is self-screening for stability. The dominant species at equilibrium are those which possess optimally packed and folded structures. The strategy is thus a fast, high-throughput technique for identifying lead sequences for de novo proteins.

The side-chain packing responsible for stabilizing protein cores is an instance of molecular recognition by which any side-chain is accomodated by those around it. We are extending this idea by designing proteins whose hydrophobic cores contain a patterned cavity that can recognize and bind small molecules. Such proteins can then be engineered to create recognition arrays on surfaces. In this way we hope to construct sensors for clinical and environmental diagnostic applications.

Selected Publications

Roy, L.; Case, M. A. Recursively enriched dynamic combinatorial libraries for the self-selection of optimally stable proteins. J. Phys. Chem. B 2011, 115, 2454-2464.

Roy, L.; Case, M. A. Protein core packing by dynamic combinatorial chemistry. J. Am. Chem. Soc. 2010, 132, 999-999.

Roy, L.; Case, M. A. Electrostatic determinants of stability in parallel 3-stranded coiled coils. Chem. Comm. 2009, 192-194.

Richardson, A.; Banerjee, S.; Wright, J.; Case, M.; Savin, D. Transition metal binding in designed peptide block copolymer micelles. Polym. Mater. Sci. Eng. 2007, 97, 38.

Balakrishnan, G.; Hu, Y.; Case, M. A.; Spiro, T. G. Microsecond melting of a folding intermediate in a coiled-coil peptide, monitored by T-jump/UV Raman spectroscopy. J. Phys. Chem. B 2006, 110, 19877-19883.

Case, M. A.; McLendon, G. L. Metal-assembled modular proteins: toward functional protein design. Accts. Chem. Res. 2004, 37, 754-762.

Balakrishnan, G.; Case, M. A.; Pevsner, A.; Zhao, X. J.; Tengroth, C.; McLendon, G. L.; Spiro, T. G. Time-resolved absorption and UV resonance Raman spectra reveal stepwise formation of T quaternary contacts in the allosteric pathway of hemoglobin. J. Mol. Biol. 2004, 340, 843-856.

Balakrishnan, G.; Tsai, C.-H.; Wu, Q.; Case, M. A.; Pevsner, A.; McLendon, G. L.; Ho, C.; Spiro, T. G. Hemoglobin site-mutants reveal dynamical role of interhelical H-bonds in the allosteric pathway: time-resolved UV resonance Raman evidence for intra-dimer coupling. J. Mol. Biol. 2004, 340, 857-868.

Puranik, M.; Nielsen, S. B.; Youn, H.; Hvitved, A. N.; Bourassa, J. L.; Case, M. A.; Tengroth, C.; Balakrishnan, G.; Thorsteinsson, M. V.; Groves, J. T.; McLendon, G. L.; Roberts, G. P.; Olson, J. S.; Spiro, T. G. Dynamics of carbon monoxide binding to CooA. J. Biol. Chem. 2004, 279, 21096-21108.

Doerr, A. J.; Case, M. A.; Pelczer, I.; McLendon, G. L. Design of a functional protein for molecular recognition: specificity of ligand binding in a metal-assembled protein cavity probed by 19F NMR. J. Am. Chem. Soc. 2004, 126, 4192-4198.

Ren, Y.; Wang, W.-H.; Wang, Y.-H.; Case, M.; Qian, W.; McLendon, G.; Huang, Z.-X. Mapping the electron transfer interface between cytochrome b5 and cytochrome c. Biochemistry 2004, 43, 3527-3536.