title: Predicting human plasma protein binding of drugs using plasma protein interaction QSAR analysis (PPI-QSAR).
abstract: A novel method, named as the plasma protein-interaction QSAR analysis (PPI-QSAR) was used to construct the QSAR models for human plasma protein binding. The intra-molecular descriptors of drugs and inter-molecular interaction descriptors resulted from the docking simulation between drug molecules and human serum albumin were included as independent variables in this method. A structure-based in silico model for a data set of 65 antibiotic drugs was constructed by the multiple linear regression method and validated by the residual analysis, the normal Probability-Probability plot and Williams plot. The R(2) and Q(2) values of the entire data set were 0.87 and 0.77, respectively, for the training set were 0.86 and 0.72, respectively. The results indicated that the fitted model is robust, stable and satisfies all the prerequisites of the regression models. Combining intra-molecular descriptors with inter-molecular interaction descriptors between drug molecules and human serum albumin, the drug plasma protein binding could be modeled and predicted by the PPI-QSAR method successfully.
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.forename: Zhuxi
authors.initials: Z
authors.lastname: Chen
authors.forename: Xuejun
authors.initials: X
authors.lastname: Xu
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Sui
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D005544:Forecasting; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D015394:Molecular Structure; D010949:Plasma / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012984:Software
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins