Chiroptical activity of gas-phase propylene oxide predicting the handedness of interstellar circular polarization in the presolar nebula.

Propylene oxide, the first chiral molecule recently detected in the interstellar medium, has once again raised the question whether biomolecular chirality might have cosmic origins. However, accurate chiroptical properties of propylene oxide in the ultraviolet spectral range necessary to suggest possible asymmetric synthetic routes in the gas phase are scarce. Here, we report on the first experimental measurements of the anisotropy spectra of gas-phase propylene oxide in the vacuum ultraviolet spectral range. Our experimental results provide novel insights into the handedness of interstellar circular polarization at the dawn of molecular evolution of our star- and planet-forming region. Besides the fundamental importance of this new investigation for understanding the origin and evolution of homochirality on Earth, our high-resolution experimental electronic circular dichroism data will inspire new efforts in quantum computational spectroscopy.

Amino acid gas phase circular dichroism and implications for the origin of biomolecular asymmetry.

Life on Earth employs chiral amino acids in stereochemical L-form, but the cause of molecular symmetry breaking remains unknown. Chiroptical properties of amino acids - expressed in circular dichroism (CD) - have been previously investigated in solid and solution phase. However, both environments distort the intrinsic charge distribution associated with CD transitions. Here we report on CD and anisotropy spectra of amino acids recorded in the gas phase, where any asymmetry is solely determined by the genuine electromagnetic transition moments. Using a pressure- and temperature-controlled gas cell coupled to a synchrotron radiation CD spectropolarimeter, we found CD active transitions and anisotropies in the 130-280 nm range, which are rationalized by ab initio calculation. As gas phase glycine was found in a cometary coma, our data may provide insights into gas phase asymmetric photochemical reactions in the life cycle of interstellar gas and dust, at the origin of the enantiomeric selection of life's L-amino acids.

Deciphering the glycan preference of bacterial lectins by glycan array and molecular docking with validation by microcalorimetry and crystallography.

Recent advances in glycobiology revealed the essential role of lectins for deciphering the glycocode by specific recognition of carbohydrates. Integrated multiscale approaches are needed for characterizing lectin specificity: combining on one hand high-throughput analysis by glycan array experiments and systematic molecular docking of oligosaccharide libraries and on the other hand detailed analysis of the lectin/oligosaccharide interaction by x-ray crystallography, microcalorimetry and free energy calculations. The lectins LecB from Pseudomonas aeruginosa and BambL from Burkholderia ambifaria are part of the virulence factors used by the pathogenic bacteria to invade the targeted host. These two lectins are not related but both recognize fucosylated oligosaccharides such as the histo-blood group oligosaccharides of the ABH(O) and Lewis epitopes. The specificities were characterized using semi-quantitative data from glycan array and analyzed by molecular docking with the Glide software. Reliable prediction of protein/oligosaccharide structures could be obtained as validated by existing crystal structures of complexes. Additionally, the crystal structure of BambL/Lewis x was determined at 1.6 Å resolution, which confirms that Lewis x has to adopt a high-energy conformation so as to bind to this lectin. Free energies of binding were calculated using a procedure combining the Glide docking protocol followed by free energy rescoring with the Prime/Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method. The calculated data were in reasonable agreement with experimental free energies of binding obtained by titration microcalorimetry. The established predictive protocol is proposed to rationalize large sets of data such as glycan arrays and to help in lead discovery projects based on such high throughput technology.

Kinetics and thermodynamics of gas diffusion in a NiFe hydrogenase.

We have investigated O2 and H2 transport across a NiFe hydrogenase at the atomic scale by means of computational methods. The Wild Type protein has been compared with the V74Q mutant. Two distinct methodologies have been applied to study the gas access to the active site. Temperature locally enhanced sampling simulations have emphasized the importance of protein dynamics on gas diffusion. The O2 diffusion free energy profiles, obtained by umbrella sampling, are in agreement with the known kinetic data and show that in the V74Q mutant, the inhibition process is lowered from both a kinetic and a thermodynamic point of view.