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Title: Accurate determination of solvation free energies of neutral organic compounds from first principles

Journal Article · · Nature Communications
 [1];  [2];  [2];  [2];  [3];  [2]; ORCiD logo [2];  [2];  [3];  [2];  [2]; ORCiD logo [2];  [2];  [2];  [4]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [5];  [6]; ORCiD logo [5] more »; ORCiD logo [7];  [7];  [8];  [8];  [2] « less
  1. InterX Inc., Berkeley, CA (United States); OSTI
  2. InterX Inc., Berkeley, CA (United States)
  3. InterX Inc., Berkeley, CA (United States); Lomonosov Moscow State University, Moscow (Russian Federation)
  4. Carnegie Mellon Univ., Pittsburgh, PA (United States)
  5. Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials; Univ. of Illinois, Chicago, IL (United States)
  6. Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials
  7. Wayne State Univ., Detroit, MI (United States)
  8. Stanford Univ., CA (United States). School of Medicine
+ Show Author Affiliations

The main goal of molecular simulation is to accurately predict experimental observables of molecular systems. Another long-standing goal is to devise models for arbitrary neutral organic molecules with little or no reliance on experimental data. While separately these goals have been met to various degrees, for an arbitrary system of molecules they have not been achieved simultaneously. For biophysical ensembles that exist at room temperature and pressure, and where the entropic contributions are on par with interaction strengths, it is the free energies that are both most important and most difficult to predict. We compute the free energies of solvation for a diverse set of neutral organic compounds using a polarizable force field fitted entirely to ab initio calculations. The mean absolute errors (MAE) of hydration, cyclohexane solvation, and corresponding partition coefficients are 0.2 kcal/mol, 0.3 kcal/mol and 0.22 log units, i.e. within chemical accuracy. The model (ARROW FF) is multipolar, polarizable, and its accompanying simulation stack includes nuclear quantum effects (NQE). The simulation tools’ computational efficiency is on a par with current state-of-the-art packages. The construction of a wide-coverage molecular modelling toolset from first principles, together with its excellent predictive ability in the liquid phase is a major advance in biomolecular simulation.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States); Argonne National Laboratory (ANL), Argonne, IL (United States). Center for Nanoscale Materials; University of California, Los Angeles, CA (United States)
Sponsoring Organization:
InterX; USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-06CH11357; SC0021201
OSTI ID:
1904265
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 13; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Algorithms
Condensed-Phase
Force-Field
Model
Molecular-Dynamics
Performance
Protein Conformations
Water
computational chemistry
molecular dynamics
quantum chemistry