|Hoogerheide, David P
At the NIST Center for Neutron Research, neutron scattering is routinely used to study solutions and surface adsorption of biomacromolecules. Neutrons are particularly well suited to study biological materials because of their sensitivity to light constituent elements, such as H, C, and N (for a general overview see Hoogerheide, D. P., Forsyth, V. T. & Brown, K. A. 2020. Neutron scattering for structural biology. Phys Today 73, 36–42). In combination with simulation, complementary biophysical techniques such as surface plasmon resonance, and advanced data analysis techniques, neutron reflectivity has proven to have unique advantages for studying the structural biology of proteins on biomimetic bilayer lipid membrane (BLM) surfaces under physiologically relevant conditions. Successful projects have featured studies of intrinsically disordered proteins, determination of the structure of a membrane-bound protein complex, and manipulation of membrane-bound protein structure.
The bioreflectometry group collaborates with academic and government laboratories to elucidate mechanisms of protein binding to BLMs. We comprise researchers with a broad range of expertise and are actively developing advanced biochemical and biophysical techniques, particularly those useful for neutron scattering, to study membrane-associated proteins. We are interested in chemistries for new measurement platforms; protein synthesis and diagnostics; simulation methods to compare to experimental results. We are also pursuing advanced data analysis techniques and development of neutron instrumentation and sample environments in support of autonomous experimentation and high-throughput measurement for data-driven (machine learning / artificial intelligence) applications.
Hoogerheide, D. P. et al. Structural features and lipid binding domain of tubulin on biomimetic mitochondrial membranes. Proc National Acad Sci 114, E3622–E3631 (2017).
Van, Q. N. et al. Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane. Proc National Acad Sci 117, 24258–24268 (2020).
Soubias, O. et al. Membrane surface recognition by the ASAP1 PH domain and consequences for interactions with the small GTPase Arf1. Sci Adv 6, eabd1882 (2020).
Binding (biochemical); Lipid bilayers; Membrane proteins; Neutron reflectometry; Molecular dynamics simulations; Biophysical techniques; Tethered bilayer lipid membranes; Neutron instrumentation; Neutron sample environment; High-throughput measurement;