David P. Weliky

Solid–state NMR evidence for an antibody–dependent conformation of the V3 loop of HIV–1 gp120

Solid–state NMR measurements have been carried out on frozen solutions of the complex of a 24–residue peptide derived from the third variable (V3) loop of the HIV–1 envelope glycoprotein gp120 bound to the Fab fragment of an anti–gp120 antibody. The measurements place strong constraints on the conformation of the conserved central GPGR motif of the V3 loop in the antibody–bound state. In combination with earlier crystal structures of V3 peptide–antibody complexes and existing data on the cross–reactivity of the antibodies, the solid–state NMR measurements suggest that the Gly–Pro–Gly–Arg (GPGR) motif adopts an antibody–dependent conformation in the bound state and may be conformationally heterogeneous in unbound, full–length gp120. These measurements are the first application of solid–state NMR methods in a structural study of a peptide–protein complex.

Investigation of molecular structure in solids by two‐dimensional NMR exchange spectroscopy with magic angle spinning

An approach to the investigation of molecular structures in disordered solids, using two‐dimensional (2D) nuclear magnetic resonance (NMR) exchange spectroscopy with magic angle spinning (MAS), is described. This approach permits the determination of the relative orientation of two isotopically labeled chemical groups within a molecule in an unoriented sample, thus placing strong constraints on the molecular conformation. Structural information is contained in the amplitudes of crosspeaks in rotor‐synchronized 2D MAS exchange spectra that connect spinning sideband lines of the two labeled sites. The theory for calculating the amplitudes of spinning sideband crosspeaks in 2D MAS exchange spectra, in the limit of complete magnetization exchange between the labeled sites, is presented in detail. A new technique that enhances the sensitivity of 2D MAS exchange spectra to molecular structure, called orientationally weighted 2D MAS exchange spectroscopy, is introduced. Symmetry principles that underlie the cons...

High-resolution infrared spectroscopy of isotopic impurity Q1(0) transitions in solid parahydrogen

We have made a high‐resolution infrared spectroscopic study of the Q1(0) (v=1←0, J=0←0) vibrational transitions of the isotopic impurities D2 and HD in solid parahydrogen. Each impurity has a spectrum composed of ∼100 sharp lines spread over ∼0.4 cm−1. The linewidths vary, but are on the order of 10 MHz. These spectra make clear: (1) the infrared Q1(0) transitions of J=0 isotopic impurities are induced by the quadrupolar fields of nearby impurity J=1 molecules; and (2) the spectral pattern of strong Q1(0) lines is due to the splitting of the M‐orientational levels of J=1/J=0 o‐D2 or J=1/J=0 HD nearest‐neighbor (nn) impurity pairs. With the aid of several theoretical works, the strong lines in the D2 and HD spectra can be individually and unambiguously assigned as specific quantum state Q1(0) transitions of nn impurity pairs containing p‐D2/o‐D2 or o‐H2/o‐D2, and o‐H2/HD, respectively. The assigned transitions of nn impurity pairs containing o‐H2 are confirmed by combination differences which agree to with...