Structure of aqueous proline via parallel tempering molecular dynamics and neutron diffraction

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Biophysics

Background:

• The structural organization of aqueous L-proline remains debated, with various models proposing different degrees of local and long-range correlations.
• Understanding these structures is crucial for comprehending proline's role in biological systems and chemical processes.

Purpose of the Study:

• To investigate the structure of aqueous L-proline using advanced simulation techniques.
• To compare simulation results with experimental neutron diffraction and small-angle neutron scattering (SANS) data.
• To evaluate the performance of different water and force field models in reproducing experimental observations.

Main Methods:

• Atomistic, replica exchange molecular dynamics (MD) simulations were employed.
• Simulations were validated against recent neutron diffraction and SANS data.
• The static structure factor S(Q) was computed and compared across various isotopic compositions and water models (TIP3P, TIP4P, SPC/E) with the CHARMM22 force field.
• Approximate quantum corrections from gas-phase path integral simulations were applied.

Main Results:

• Reasonably good agreement was achieved between simulations and neutron experiments across the Q range, though model-dependent variations were observed.
• Local structures, including dimers and short oligomeric chains stabilized by hydrogen bonds (often bifurcated) and hydrophobic contacts, were identified as dominant motifs.
• Evidence for significant long-range association was equivocal; no spontaneous long-range structures formed in MD, and SANS data lacked clear low-Q signatures.
• Artificially imposed long-range structures were annealed out in simulations, though some small residual aggregates persisted.

Conclusions:

• Molecular dynamics simulations, when compared with neutron scattering experiments, provide insights into the local and long-range structure of aqueous L-proline.
• Local hydrogen-bonded and hydrophobic interactions are key features of aqueous proline solutions.
• While significant long-range order is not spontaneously observed, the persistence of small aggregates suggests a degree of order beyond that directly apparent in SANS data.