A simplified model to predict P-glycoprotein interacting drugs from 3D molecular interaction field.
A new two components partial least squares discriminant analysis (PLS) model for the prediction of P-glycoprotein-associated ATPase activity of drugs by using VolSurf compute theoretical molecular descriptors derived from 3D molecular interaction field was reported in the present study. By using 27 diverse drugs from literature, two models were constructed (R(2)=0.9003, 0.8150; Q(2)=0.7165, 0.7630) in this paper, which were similar to models that utilized MolSurf parametrization (R(2)=0.7760, 0.7180; Q(2)=0.7420, 0.6950) by using 22 drugs reported in the same literature. The results investigated VolSurf software was superior to MolSurf in its simplicity. Properties associated with the volume, polarizability, and hydrogen bond could have important impact on the P-glycoprotein-associated ATPase activity.
Zhuang
Xiao-Mei
XM
Beijing Institute of Pharmacology and Toxicology, Beijing, China 100850.
Xiao
Jun-Hai
JH
Li
Jin-Tong
JT
Zhang
Zhen-Qing
ZQ
Ruan
Jin-Xiu
JX
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry*; D000251:Adenosine Triphosphatases / Q000737:chemistry; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004364:Pharmaceutical Preparations; D000251:Adenosine Triphosphatases