Structure of Aqueous Proline via Parallel Tempering Molecular Dynamics and Neutron Diffraction

Abstract

The structure of aqueous L-proline amino acid has been the subject of much debate centering on the validity of various proposed models, differing widely in the extent to which local and long-range correlations are present. Here, aqueous proline is investigated by atomistic, replica exchange molecular dynamics simulations, and the results are compared to neutron diffraction and small angle neutron scattering (SANS) data, which have been reported recently (McLain, S.; Soper, A.; Terry, A.; Watts, A. J. Phys. Chem. B 2007, 111, 4568). Comparisons between neutron experiments and simulation are made via the static structure factor S(Q) which is measured and computed from several systems with different H/D isotopic compositions at a concentration of 1:20 molar ratio. Several different empirical water models (TIP3P, TIP4P, and SPC/E) in conjunction with the CHARMM22 force field are investigated. Agreement between experiment and simulation is reasonably good across the entire Q range although there are significant model-dependent variations in some cases. In general, agreement is improved slightly upon application of approximate quantum corrections obtained from gas-phase path integral simulations. Dimers and short oligomeric chains formed by hydrogen bonds (frequently bifurcated) coexist with apolar (hydrophobic) contacts. These emerge as the dominant local motifs in the mixture. Evidence for long-range association is more equivocal: No long-range structures form spontaneously in the MD simulations, and no obvious low-Q signature is seen in the SANS data. Moreover, associations introduced artificially to replicate a long-standing proposed mesoscale structure for proline correlations as an initial condition are annealed out by parallel tempering MD simulations. However, some small residual aggregates do remain, implying a greater degree of long-range order than is apparent in the SANS data.

Stabilizing effect of TMAO on globular PNIPAM states: preferential attraction induces preferential hydration

“…56,57 In contrast to these assumptions, our results indicate that protectants like TMAO preferentially accumulate around macromolecules which results in a preferential hydration of PNIPAM due to the strong kosmotropic and hygroscopic properties of TMAO. In fact, this mechanism, which was suggested for other co-solutes like cryoprotectants, 58,59 is in good agreement with the experimental results and allows us a qualitative explanation and interpretation of the DLS measurements. We also studied the influence of urea on PNIPAM by DLS experiments which additionally verifies our proposed mechanism due to the observed deviations from the results found for TMAO.…”

Combining wide-angle and small-angle scattering to study colloids and self-assembly

“…Both SANS and wideangle scattering studies were carried out on the same solutions and although the formation of larger transient clusters of proline [38,39] and glutamine [40] were observed during modelling of the wide angle scattering data and in MD simulations, no larger scale structures were found in the SANS data.…”

Evidence for cooperative Na+ and Cl− binding by strongly hydrated l-proline

“…9) the dipole moments of the two constituting Pro molecules should be practically anti-parallel. Based on results from various techniques Troitzsch et al 16,18,19 also found evidence for dimeric structures at high Pro concentrations, in particular at low temperature. However, they found no evidence for mesoscale aggregation postulated on the basis of spectroscopic and calorimetric data.…”

“…Despite considerable efforts during the last decade to understand Pro-water interactions only a few publications describe its hydration structure. 6,7,[15][16][17][18][19][20][21][22][23][24][25] Moreover, the available quantitative information is scattered considerably. For instance, hydration numbers range from 20, obtained in a MD simulation, 15 to 11-12 from statistical mechanics 23 to 8-9, obtained with neutron diffraction.…”

“…17 Although the importance of hydrogen bonding is well documented, information on the number and strength of the formed ProÁ Á ÁH 2 O H-bonds is contradictory. 8,13,[16][17][18][19]26 Obviously, the current understanding of Pro hydration and thus of its action as a bioprotectant is still insufficient and current knowledge on ion binding is even more patchy. Complementing previous investigations of the Ivanovo group, [23][24][25] the present contribution aims to improve this situation by combining the complementary approaches of broadband dielectric relaxation spectroscopy 27,28 (DRS) and statistical mechanics calculations in the framework of the reference interaction site model (RISM) integral equation theory.…”