The energy landscape is analyzed for off-lattice bead models of protein L and protein G as a function of a static pulling force. Two different pairs of attachment points (pulling directions) are compared in each case, namely, residues 1/56 and 10/32. For the terminal residue pulling direction 1/56, the distinct global minimum structures are all extended, aside from the compact geometry that correlates with zero force. The helical turns finally disappear at the highest pulling forces considered. For the 10/32 pulling direction, the changes are more complicated, with a variety of competing arrangements for beads outside the region where the force is directly applied. These alternatives produce frustrated energy landscapes, with low-lying minima separated by high barriers. The calculated folding pathways in the absence of force are in good agreement with previous work. The N-terminal hairpin folds first for protein L and the C-terminal hairpin for protein G, which exhibits an intermediate. However, for a relatively low static force, where the global minimum retains its structure, the folding mechanisms change, sometimes dramatically, depending on the protein and the attachment points. The scaling relations predicted by catastrophe theory are found to hold in the limit of short path lengths.

Organic molecules can be stable in distinct crystalline forms, known as polymorphs, which have significant consequences for industrial applications. Here, we predict the polymorphs of crystalline benzene computationally for an accurate anisotropic model parametrized to reproduce electronic structure calculations. We adapt the basin-hopping global optimization procedure to the case of crystalline unit cells, simultaneously optimizing the molecular coordinates and unit cell parameters to locate multiple low-energy structures from a variety of crystal space groups. We rapidly locate all the well-established experimental polymorphs of benzene, each of which corresponds to a single local energy minimum of the model. Our results show that basin-hopping can be both an efficient and effective tool for polymorphic crystal structure prediction, requiring no a priori experimental knowledge of cell parameters or symmetry.

Polariton chemistry holds promise for facilitating mode-selective chemical reactions, but the underlying mechanism behind the rate modifications observed under strong vibrational coupling is not well understood. Using the recently developed quantum transition path theory, we have uncovered a mechanism of resonant suppression of a thermal reaction rate in a simple model polaritonic system consisting of a reactive mode in a bath confined to a lossless microcavity with a single photon mode. We observed the formation of a polariton during rate-limiting transitions on reactive pathways and identified the concomitant rate suppression as being due to hybridization between the reactive mode and the cavity mode, which inhibits bath-mediated tunneling. The transition probabilities that define the quantum master equation can be directly translated into a visualization of the corresponding polariton energy landscape. This landscape exhibits a double funnel structure with a large barrier between the initial and final states.

Clusters of eight water molecules play an important role in theoretical analysis of aqueous structure and dynamics but have proven to be challenging experimental targets. Here we report the high-resolution spectroscopic characterization of the water octamer. Terahertz (THz) vibration-rotation-tunneling (VRT) spectroscopy resolved 99 transitions with 1 part per million precision in a narrow range near 46.5 wave numbers, which were assigned to the h16 octamer via detailed isotope dilution experiments. Fitting to a semi-rigid symmetric top model supports predictions of two coexisting cuboidal structures and provides precise values for the changes in their rotational constants. Comparison with theory and previous spectroscopic data provides a characterization of the two structures and the observed torsional vibration and supports the prediction that the D2d symmetry structure is lower in energy than the S4 isomer.

We report a combined theoretical and experimental study of the water octamer-h16. The calculations used the ring-polymer instanton method to compute tunnelling paths and splittings in full dimensionality. The experiments measured extensive high resolution spectra near 1.4 THz, for which isotope dilution experiments and group theoretical analysis support assignment to the octamer. Transitions appear as singlets, consistent with the instanton paths, which involve the breakage of two hydrogen-bonds and thus give tunneling splittings below experimental resolution.

We report the assignment and analysis of 176 transitions belonging to a librational band of the (H₂O)₆ cage isomer near 525 cm^-1(15 THz). From a fit of the transitions to an asymmetric top model, we observe both dramatic changes in the rotational constants relative to the ground state, indicating significant nonrigidity, and striking enhancement in the tunneling motions that break and reform the hydrogen bonds in the cluster. This is the fifth water cluster system to display such an enhancement in the 15 THz librational region, the details of which may help to elucidate the hydrogen bond dynamics occurring in bulk liquid water.

Using diode laser vibration-rotation-tunneling spectroscopy near 15 Thz (500 cm-1), we have measured and assigned 142 transitions to three a-type librational subbands of the water hexamer-d12 prism. These subbands reveal dramatically enhanced (ca. 1000×) tunneling splittings relative to the ground state. This enhancement is in agreement with that observed for the water dimer, trimer, and pentamer in this same frequency region. The water prism tunneling motion has been predicted to potentially describe the motions of water in interfacial and confined environments; hence, the results presented here indicate that excitation of librational vibrations has a significant impact on the hydrogen bond dynamics in these macroscopic environments.

Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.