Protein Dynamics


For most enzymes and drug targets, ligand binding is associated with the motion of a flexible loop or domain and conformational changes. We investigate the characteristic timescales of an active-site loop motion in the protein TIM. Similarly, metal-substrate geometry and conformational exchange rates are studied for metalloenzymes, such as the drug target cytochrome P450. An advantage of solid-state NMR is the presence of anisotropic interactions such as dipolar, quadrupolar, and chemical shift anisotropy (CSA), which are an abundant source of information for proteins dynamics. Currently, we investigate slow conformational change (millisecond-to-second timescale) by refocusing dipolar interactions through a very high-efficiency 1D dynamics detection scheme (CODEX), described by Schmidt-Rohr. We also study intermediate timescale (millisecond-to-microsecond) through T1ρ measurements monitoring the motion of CSA tensors. The quantitative application of these techniques to proteins and the design of original new pulse sequences are two main directions of our research


McDermott Group Publications

  1. Li, W.. and McDermott, Ann. E. "Detection of slow dynamics by solid-state NMR: Application to L-phenylalanine hydrochloride" 2013. Concepts in Magnetic Resonance Part A: Bridging Education and Research 42 A :14-22 link info
  2. Li, W.. and McDermott, Ann. E. "Investigation of slow molecular dynamics using R-CODEX" 2012. Journal of Magnetic Resonance 222 :74-80 link info
  3. Quinn, C.. and McDermott, Ann. E. "Quantifying conformational dynamics using solid-state R1ρ experiments" 2012. Journal of Magnetic Resonance 222 :1-7 link info