Chris Neale

PhD candidate
Tel.: (416) 813-6855
email: chris.neale |at| utoronto.ca

Research

• Solvation and Binding of the Outer Membrane Enzyme PagP by Detergents and Lipids. The gram negative integral outer membrane protein PagP increases virulence of bacteria by providing non-specific resistance to host cationic anti-microbial peptides (CAMPs) and by converting lipid A from an agonist to an antagonist of host immune response signaling. If the mechanism of PagP substrate entry can be determined, the door is open for rational drug design. I am currently doing molecular dynamics simulations in order to determine the pathway by which the SN-1 acyl chain of a donor phospholipid binds PagP. I am also investigating the dynamics of PagP in different hydrophobic solvents.

Publications

• N. Chakrabarti, C. Neale, J. Payandeh, E. F. Pai, and R. Pomès, "An Iris-Like Mechanism of Pore Dilation in the CorA Magnesium Transport System", Biophys. J., 98(5):784-792 (2010).
• S. Rauscher, C. Neale, and R. Pomès, "Simulated Tempering Distributed Replica Sampling, Virtual Replica Exchange, and Other Generalized-Ensemble Methods for Conformational Sampling", J. Chem. Theory Comput., 5(10):2640-2662 (2009).
• M. S. Al-Abdul-Wahid, C. Neale, R. Pomès, and R. S, Prosser, "A Solution NMR Approach to the Measurement of Amphiphile Immersion Depth and Orientation in Membrane Model Systems", J. Am. Chem. Soc., 131, 6452-6459 (2009).
• C. Neale, T. Rodinger, and R. Pomès, "Equilibrium exchange enhances the convergence rate of umbrella sampling", Chemical Physics Letters 460, 375-381 (2008).
• M. A. Khan, C. Neale, C. Michaux, R. Pomès, G. G. Privé, R. W. Woody, and R. E. Bishop, "Gauging a hydrocarbon ruler by an intrinsic exciton probe", Biochemistry 46, 4565-4579 (2007).
• J.A. Marsh, C. Neale, F.E. Jack FE, WY. Choy, A.Y. Lee, K.A. Crowhurst, and J.D. Forman-Kay, "Improved Structural Characterizations of the drkN SH3 Domain Unfolded State Suggest a Compact Ensemble with Native-like and Non-native Structure." J. Mol. Biol., 367, 1494-1510 (2007)
• M. Tollinger, C. Neale, L.E. Kay, and J.D. Forman-Kay, "Characterization of the Hydrodynamic Properties of the Folding Transition State of an SH3 Domain by Magnetization Transfer NMR Spectroscopy" Biochemistry, 45, 6434 -6445 (2006)
• L.X. Wu, J. La Rose, L. Chen, C. Neale, T. Mak, K. Okkenhaug, R. Wange, and R. Rottapel, "CD28 Regulates the Translation of Bcl-xL via the Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Pathway" J. Immunology, 174, 180-194 (2005)
• R. Rottapel, S. Ilangumaran, C. Neale, J. La Rose, J.M-Y Ho, M.H-H Nguyen, D. Barber, P. Dubreuil, and P. de Sepulveda, "The tumor suppressor activity of SOCS-1" Oncogene, 21, 4351-4362 (2002)

Detailed Methodological Testing

A Method to Combine OPLS Protein with Berger Lipids