Predictive Models for the Free Energy of Hydrogen Bonded Complexes with Single and Cooperative Hydrogen Bondsстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 3 декабря 2017 г.
Авторы:
Glavatskikh M.,
Madzhidov T.,
Solov’ev V.,
Marcou G.,
Horvath D.,
Varnek A.
Аннотация:In this work, we report QSPR modeling of the
free energy DG of 1:1 hydrogen bond complexes of differ-
ent H-bond acceptors and donors. The modeling was per-
formed on a large and structurally diverse set of 3373 com-
plexes featuring a single hydrogen bond, for which DG was
measured at 298 K in CCl4. The models were prepared
using Support Vector Machine and Multiple Linear Regres-
sion, with ISIDA fragment descriptors. The marked atoms
strategy was applied at fragmentation stage, in order to
capture the location of H-bond donor and acceptor centers.
Different strategies of model validation have been suggest-
ed, including the targeted omission of individual H-bond
acceptors and donors from the training set, in order to
check whether the predictive ability of the model is not
limited to the interpolation of H-bond strength between
two already encountered partners. Successfully cross-vali-
dating individual models were combined into a consensus
model, and challenged to predict external test sets of 629
and 12 complexes, in which donor and acceptor formed
single and cooperative H-bonds, respectively. In all cases,
SVM models outperform MLR. The SVM consensus model
performs well both in 3-fold cross-validation (RMSE=
1.50 kJ/mol), and on the external test sets containing com-
plexes with single (RMSE=3.20 kJ/mol) and cooperative H-
bonds (RMSE=1.63 kJ/mol).