Journal
JOURNAL OF PHYSICAL CHEMISTRY B
Volume 116, Issue 15, Pages 4524-4534Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jp2118373
Keywords
-
Categories
Funding
- Office of Science of the U.S. Department of Energy [DE-AC02-05CH11231]
Ask authors/readers for more resources
An accurate representation of solute-water interactions is necessary for molecular dynamics simulations of biomolecules that reside in aqueous environments. Modern force fields and advanced water models describe solute-solute and water-water interactions reasonably accurately but have known shortcomings in describing solute-water interactions, demonstrated by the large differences between calculated and experimental solvation free energies across a range of peptide and drug chemistries. In this work, we introduce a method for optimizing solute-water van der Waals interactions to reproduce experimental solvation free energy data and apply it to the optimization of a fixed charge force field (AMBER ff99SB/GAFF) and advanced water model (TIP4P-Ew). We show that, with these optimizations, the combination of AMBER ff99SB/GAFF and TIP4P-Ew is able to reproduce the solvation free energies of a variety of biologically relevant small molecules to within 1.0 k(B)T. We further validate these optimizations by examining the aggregation propensities of dipeptide-water solutions, the conformational preferences of short disordered peptides, and the native state stability and dynamics of a folded protein.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available