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Ph.D. University of Pennsylvania (1984) 905 Stellar-Chance Laboratories |
Dr. Wand's research focuses on exploring the relationships between static structure, structural dynamics and function in a range of protein systems. Current efforts are centered on calmodulin, a main player in calcium-mediated signal transduction, a variety of heme-binding proteins, interleukins and their receptors, and ubiquitin. The interaction of calmodulin with several target proteins is being investigated by high resolution multidimensional multinuclear NMR methods with an aim of discovering the full range of interactions displayed by this main player in calcium-mediated signal transduction. A key concept is the balance between changes in structure (enthalpy) and dynamics (entropy) is the binding process. A range of other systems involving protein-protein interactions as well as interactions with small ligands are also being pursued. Through these studies a remarkably rich manifold of fast dynamical modes have been revealed and a surprising functional role for them discovered. The Wand lab is also committed to continuing improvement and development of novel NMR techniques. They have recently focused on high pressure NMR to probe the protein ensemble, NMR relaxation methods to measure conformational dynamics throughout the protein and a novel method to approach large soluble, unstable and membrane proteins by solution NMR methods. The latter approach involves the use of reverse micelle encapsulation to provide a protective environment for proteins to allow them to be dissolved in low viscosity fluids such as liquid ethane. The initial idea was to use the low viscosity of ethane to overcome the slow tumbling problem for solution NMR spectroscopy presented by large protein in water. Applications have since been expanded to studies of proteins of marginal stability by employing the confined space of the reverse micelle, suppression of protein aggregation to allow study of intermediates of aggregation such as occur in amyloid formation, and studies of membrane proteins. Selected Publications: Frederick, K.K., M.S. Marlow, K.G. Valentine, and A.J. Wand (2007) Conformational entropy in molecular recognition by proteins. Nature 448:325-329. Song, X.- J., P.F. Flynn, K.A. Sharp, and A.J. Wand (2007) Temperature dependence of fast dynamics in proteins. Biophys. J. 92:L43-45. Igumenova, T.I. , K.K. Frederick, and A.J. Wand (2006) Characterization of the fast dynamics of protein amino acid side chains using NMR relaxation in solution. Chem. Rev. 106(5):1672-1699. Whitten, S.T., A.J. Kurtz., M.S. Pometun, A.J. Wand, and V.J. Hilser (2006) Revealing the nature of the native state ensemble through cold denaturation. Biochemistry 45:10163-10174. Marlow, M.S. and A.J. Wand (2006) Conformational dynamics of calmodulin in complex with the calmodulin-dependent kinase kinase alpha calmodulin-binding domain. Biochemistry 45:8732-8741. Frederick, K.K., J.K. Kranz, and A.J. Wand (2006) Characterization of the backbone and side chain dynamics of the CaM:CaMKIp complex reveals microscopic contributions to protein conformational entropy. Biochemistry 45:9841-9848. Pometun, M.S., R.W. Peterson, C.R. Babu, and A.J. Wand, (2006) Cold denaturation of encapsulated ubiquitin. J. Am. Chem. Soc. 128:10652-10653. Wang, T., K.K. Frederick, T.I. Igumenova, A.J. Wand, and E.R.P. Zuiderweg (2005) Changes in calmodulin main-chain dynamics upon ligand binding revealed by cross-correlated NMR relaxation measurements. J. Am. Chem. Soc. 127:828-829. Zech, S.G., A.J. Wand, and A.E. McDermott (2005) Protein structure determination by high-resolution solid-state NMR spectroscopy: Application to microcrystalline ubiquitin. J. Am. Chem. Soc. 127:8618-8626. Peterson, R.W., B.G. Lefebvre, and A.J. Wand (2005) High resolution NMR studies of encapsulated proteins in liquid ethane. J. Am. Chem. Soc. 127:10176-10177. Igumenova, T.I., A.L. Lee, and A.J. Wand (2005) Backbone and sidechain dynamics of mutant calmodulin-peptide complexes. Biochemistry 44:12627-12639. Peterson, R.W., M.S. Pometun, Z. Shi, and A.J. Wand (2005) Novel surfactant mixtures for NMR spectroscopy of encapsulated proteins dissolved in low viscosity fluids. Prot. Sci. 14:2919-2921. Peterson, R.W. and A.J. Wand (2005) Self contained high pressure cell, apparatus and procedure for the preparation of encapsulated proteins dissolved in low viscosity fluids for NMR spectroscopy. Rev. Sci. Instr. 76 Art. No. 094101. |
