TY - JOUR
T1 - Diameter is a key 3D characteristic for assessments of efficient inhibitors of protein-protein interactions
AU - Nakadai, Masakazu
AU - Tomida, Shuta
N1 - Funding Information:
This work was partially supported by JSPS KAKENHI (Grant-in-Aid for Scientific Research (B) for S.T.) grant number JP20H03771.
Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/10/26
Y1 - 2020/10/26
N2 - Three-dimensional (3D) molecular descriptors, including physicochemical and shape properties, for protein-protein interaction (PPI) interface inhibitors have become a topic of discussion. However, the relationships between such properties and binding free energy have not been adequately investigated. In this study, we focused on identifying key 3D molecular descriptors related to the binding free energy and/or the ligand efficiency (LE) of PPI interface inhibitors. A positive correlation was found between the binding free energy and the diameter (D) of cylindrical 3D molecules, in addition to a correlation between LE and D/heavy atom count (HAC). In addition, we showed a correlation between LE and D/HAC for macrocyclic compounds, suggesting that the present findings could be applied during assessments of the potential of macrocyclic PPI interface inhibitors in drug discovery processes.
AB - Three-dimensional (3D) molecular descriptors, including physicochemical and shape properties, for protein-protein interaction (PPI) interface inhibitors have become a topic of discussion. However, the relationships between such properties and binding free energy have not been adequately investigated. In this study, we focused on identifying key 3D molecular descriptors related to the binding free energy and/or the ligand efficiency (LE) of PPI interface inhibitors. A positive correlation was found between the binding free energy and the diameter (D) of cylindrical 3D molecules, in addition to a correlation between LE and D/heavy atom count (HAC). In addition, we showed a correlation between LE and D/HAC for macrocyclic compounds, suggesting that the present findings could be applied during assessments of the potential of macrocyclic PPI interface inhibitors in drug discovery processes.
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U2 - 10.1021/acs.jcim.0c00607
DO - 10.1021/acs.jcim.0c00607
M3 - Article
C2 - 32808775
AN - SCOPUS:85094684953
VL - 60
SP - 4785
EP - 4790
JO - Journal of Chemical Documentation
JF - Journal of Chemical Documentation
SN - 1549-9596
IS - 10
ER -