The vertebrate eye lens contains high concentrations of crystallins. The dense lenses of fish are particularly abundant in a class called γM-crystallin whose members are characterized by an unusually high methionine content and partial loss of the four tryptophan residues conserved in all γ-crystallins from mammals which are proposed to contribute to protection from UV-damage. Here, we present the structure and dynamics of γM7-crystallin from zebrafish (Danio rerio). The solution structure shares the typical two-domain, four-Greek-key motif arrangement of other γ-crystallins, with the major difference noted in the final loop of the N-terminal domain, spanning residues 65–72. This is likely due to the absence of the conserved tryptophans. Many of the methionine residues are exposed on the surface but are mostly well-ordered and frequently have contacts with aromatic side chains. This may contribute to the specialized surface properties of these proteins that exist under high molecular crowding in the fish lens. NMR relaxation data show increased backbone conformational motions in the loop regions of γM7 compared to those of mouse γS-crystallin and show that fast internal motion of the interdomain linker in γ-crystallins correlates with linker length. Unfolding studies monitored by tryptophan fluorescence confirm results from mutant mouse γS-crystallin and show that unfolding of a βγ-crystallin domain likely starts from unfolding of the variable loop containing the more fluorescently quenched tryptophan residue, resulting in a native-like unfolding intermediate.

An extension to diffusion Monte Carlo (DMC) is proposed for simultaneous evaluation of multiple rotationally excited states of fluxional molecules. The method employs an expansion of the rotational dependence of the wave function in terms of the eigenstates of the symmetric top Hamiltonian. Within this DMC approach, each walker has a separate rotational state vector for each rotational state of interest. The values of the coefficients in the expansion of the rotational state vector associated with each walker, as well as the locations of the walkers, evolve in imaginary time under the action of a propagator based on the imaginary-time time-dependent Schrödinger equation. The approach is first applied to H3(+), H2D(+), and H3O(+) for which the calculated energies can be compared to benchmark values. For low to moderate values of J the DMC results are found to be accurate to within the evaluated statistical uncertainty. The rotational dependence of the vibrational part of the wave function is also investigated, and significant rotation–vibration interaction is observed. Based on the successful application of this approach to H3(+), H2D(+), and H3O(+), the method was applied to calculations of the rotational energies and wave functions for CH5(+) with v = 0 and J ≤ 10. Based on these calculations, the rotational energy progression is shown to be consistent with that for a nearly spherical top molecule, and little evidence of rotation–vibration interaction is found in the vibrational wave function.

In this work the efficacy of a combined approach for capturing rovibrational coupling is investigated. Specifically, the multi-state rotational DMC method is used in combination with fixed-node DMC in a study of the rotation vibration energy levels of H 2 D + and HD + 2 . Analysis of the results of these calculations shows very good agreement between the calculated energies and previously reported values. Where differences are found, they can be attributed to Coriolis couplings, which are large in these ions and which are not fully accounted for in this approach. 2 molecules that undergo large amplitude motions provides a significant chal-3 lenge to many theoretical approaches. When vibrations are small amplitude, 4 perturbation theory provides an attractive alternative, even for highly vibra-5 tionally excited states [1, 2]. On the other hand, molecules that undergo large 6 amplitude motions sample broad regions of the potential surface. As such, 7 expansions based on a zero-order reference structure become challenging, and 8 perturbatin theory can provide unphysical results. Significant advances have 9 been made for studies of triatomic molecules, including H + 3 and its deuter-10 ated analogues for which accurate rotation/vibration energy levels have been 11 reported [3, 4]. Carrington and co-workers have made a variety of advances 12 that allow for the evaluation of vibrational energy levels and wave functions 13 for larger systems [5, 6] including the highly fluxional CH + 5 [7]. Recently 14 Fabri et al reported energies for rotationally excited states of low-lying vi-15 brational levels of H + 5 [8]. The multi-configurational time-dependent Hartree 16 approach (MCTDH) has also shown significant promise for studies of this 17 class of molecular systems [9, 10]. Wodraszka and Manthe reported results 18 of MCTDH calculations of energies of CH + 5 with J ≤ 2 [11] A challenge that 19comes in applying these approaches comes from the fact that the convergence 20 properties can be very sensitive to the choice of coordinates. 21Over the past several years, several groups have explored approaches based 22 on diffusion Monte Carlo (DMC) [12, 13] for evaluating either rotational or 23 vibrational excited states of molecules that undergo large amplitude vibra-24 tional motions even in their ground states [14, 15, 16, 17]. Systems that we 25

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