Systematic Optimization of a Fragment-Based Force Field against Experimental
Pure-Liquid Properties Considering Large Compound Families: Application
to Saturated Haloalkanes
Posted on 2020-11-24 - 16:42
Direct
optimization against experimental condensed-phase properties concerning
small organic molecules still represents the most reliable way to
calibrate the empirical parameters of a force field. However, compared
to a corresponding calibration against quantum-mechanical (QM) calculations
concerning isolated molecules, this approach is typically very tedious
and time-consuming. The present article describes an integrated scheme
for the automated refinement of force-field parameters against experimental
condensed-phase data, considering entire classes of organic molecules
constructed using a fragment library via combinatorial
isomer enumeration. The main steps of the scheme, referred to as CombiFF,
are as follows: (i) definition of a molecule family; (ii) combinatorial
enumeration of all isomers; (iii) query for experimental data; (iv)
automatic construction of the molecular topologies by fragment assembly;
and (v) iterative refinement of the force-field parameters considering
the entire family. As a first application, CombiFF is used here to
design a GROMOS-compatible united-atom force field for the saturated
acyclic haloalkane family. This force field relies on an electronegativity-equalization
scheme for the atomic partial charges and involves no specific terms
for σ-holes and halogen bonding. A total of 749 experimental
liquid densities ρliq and vaporization enthalpies
ΔHvap concerning 486 haloalkanes
are considered for calibration and validation. The resulting root-mean-square
deviations from experiment are 49.8 (27.6) kg·m–3 for ρliq and 2.7 (1.8) kJ·mol–1 for ΔHvap for the calibration
(validation) set. The values are lower for the validation set which
contains larger molecules (stronger influence of purely aliphatic
interactions). The trends in the optimized parameters along the halogen
series and across the compound family are in line with chemical intuition
based on considerations related to size, polarizability, softness,
electronegativity, induction, and hyperconjugation. This observation
is particularly remarkable considering that the force-field calibration
did not involve any QM calculation. Once the time-consuming task of
target-data selection/curation has been performed, the optimization
of a force field only takes a few days. As a result, CombiFF enables
an easy assessment of the consequences of functional-form decisions
on the accuracy of a force field at an optimal level of parametrization.
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Oliveira, Marina P.; Andrey, Maurice; Rieder, Salomé R.; Kern, Leyla; Hahn, David F.; Riniker, Sereina; et al. (2020). Systematic Optimization of a Fragment-Based Force Field against Experimental
Pure-Liquid Properties Considering Large Compound Families: Application
to Saturated Haloalkanes. ACS Publications. Collection. https://doi.org/10.1021/acs.jctc.0c00683
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AUTHORS (8)
MO
Marina P. Oliveira
MA
Maurice Andrey
SR
Salomé R. Rieder
LK
Leyla Kern
DH
David F. Hahn
SR
Sereina Riniker
BH
Bruno A. C. Horta
PH
Philippe H. Hünenberger
KEYWORDS
force-field parametershalogenfragmentacyclic haloalkane familyExperimental Pure-Liquid PropertiesΔ H vapFragment-Based Force Fieldcondensed-phasedensities ρ liqvaporization enthalpies Δ H vaprefinementforce fieldschemeoptimizationcalculationGROMOS-compatible united-atom force...calibrationCombiFFmoleculedatavalidationcombinatorial isomer enumerationQM