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@ARTICLE{Dittrich:858302,
author = {Dittrich, Jonas and Schmidt, Denis and Pfleger, Christopher
and Gohlke, Holger},
title = {{C}onverging a {K}nowledge-{B}ased {S}coring {F}unction:
{D}rug{S}core2018},
journal = {Journal of chemical information and modeling},
volume = {59},
number = {1},
issn = {1549-960X},
address = {Washington, DC},
publisher = {American Chemical Society64160},
reportid = {FZJ-2018-07190},
pages = {509–521},
year = {2019},
abstract = {We present DrugScore2018, a new version of the
knowledge-based scoring functionDrugScore, which builds upon
the same formalism used to derive DrugScore, but exploits
atraining data set of nearly 40,000 X-ray complex
structures, a highly diverse and the by farlargest dataset
ever used for such an endeavour. About 2.5 times as many
pair potentials thanbefore now have a data basis required to
yield smooth potentials, and pair potentials could nowbe
derived for eight more atom types, including interactions
involving halogen atoms and metalions highly relevant for
medicinal chemistry. Probing for dependence on training data
set sizeand quality, we show that DrugScore2018 potentials
are converged. We evaluated DrugScore2018in comprehensive
scoring, ranking, docking, and screening tests on the
CASF-2013 dataset,allowing for a comparison with >30 other
scoring functions. There, DrugScore2018 showedsimilar or
improved performance in all aspects when compared to either
DrugScore,DrugScoreCSD, or DSX and was, overall, the scoring
function showing a most consistently goodperformance in
scoring, ranking, and docking tests. Applying DrugScore2018
as objectivefunction in AutoDock3 in a large-scale docking
trial, using 4,056 protein-ligand complexesfrom PDBbind
2016, reproduced a docked pose to within 2 Å RMSD to the
crystal structure $in>75\%$ of all dockings. These results
are remarkable as the DrugScore2018 potentials werederived
from crystallographic information only, without any further
adaptation using bindingaffinity or docking decoy data.
DrugScore2018 should thus be a competitive scoring
andobjective function for structure-based ligand design
purposes.},
cin = {NIC / JSC / ICS-6},
ddc = {540},
cid = {I:(DE-Juel1)NIC-20090406 / I:(DE-Juel1)JSC-20090406 /
I:(DE-Juel1)ICS-6-20110106},
pnm = {511 - Computational Science and Mathematical Methods
(POF3-511) / 553 - Physical Basis of Diseases (POF3-553) /
Forschergruppe Gohlke $(hkf7_20170501)$},
pid = {G:(DE-HGF)POF3-511 / G:(DE-HGF)POF3-553 /
$G:(DE-Juel1)hkf7_20170501$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30513206},
UT = {WOS:000457206200047},
doi = {10.1021/acs.jcim.8b00582},
url = {https://juser.fz-juelich.de/record/858302},
}