Abstract
Calculating the hydration free energy of a macromolecule in all-atom simulations has long remained a challenge, necessitating the use of models wherein the effect of the solvent is captured without explicit account of solvent degrees of freedom. This situation has changed with developments in the molecular quasi-chemical theory (QCT)─an approach that enables calculation of the hydration free energy of macromolecules within all-atom simulations at the same resolution as is possible for small molecular solutes. The theory also provides a rigorous and physically transparent framework to conceptualize and model interactions in molecular solutions and thus provides a convenient framework to investigate the assumptions in implicit solvent models. In this study, we compare the results using molecular QCT versus predictions from EEF1, ABSINTH, and GB/SA implicit solvent models for polyglycine and polyalanine solutes covering a range of chain lengths and conformations. The hydration free energies or the differences in hydration free energies between conformers obtained from the implicit solvent models do not agree with explicit solvent results, with the deviations being largest for the group additive EEF1 and ABSINTH models. GB/SA does better in capturing the qualitative trends seen in explicit solvent results. Analysis founded on QCT reveals the critical importance of the cooperativity of hydration that is inherent in the hydrophilic and hydrophobic contributions to hydration─physics that is not well captured in additive models but somewhat better accounted for by means of a dielectric in the GB/SA approach.
| Original language | English |
|---|---|
| Pages (from-to) | 9607-9616 |
| Number of pages | 10 |
| Journal | Journal of Physical Chemistry B |
| Volume | 126 |
| Issue number | 46 |
| DOIs | |
| State | Published - Nov 24 2022 |
Funding
We gratefully acknowledge the Robert A. Welch foundation (Grant C-1241) for their financial support. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract DE-AC02-05CH11231. We also gratefully acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin (URL: http://www.tacc.utexas.edu ) for providing HPC resources. Research at Oak Ridge National Laboratory is supported under contract DE-AC05-00OR22725 from the U.S. Department of Energy to UT-Battelle, LLC.