Molecular modeling of two CYP2C19 SNPs and its implications for personalized drug design.
CYP2C19 is an important member of the cytochrome P-450 enzyme superfamily and plays a significant role in the drug metabolism. In order to gain insights for developing personalized drugs, the structure-activity relationships of two SNPs, W120R and I331V, with the ligands of CEC, Fluvoxamine, Lescol and Ticlopidine were investigated through the structure-activity relationship approach. By means of a series of docking studies, the binding pockets of the two SNPs for the four compounds are explicitly defined that will be very useful for conducting mutagenesis studies, providing insights into personalization of drug treatments and stimulating novel strategies for finding desired personalized drugs.
Wang
Jing-Fang
JF
Bioinformatic Center, Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Wei
Dong-Qing
DQ
Chen
Chao
C
Li
Yixue
Y
Chou
Kuo-Chen
KC
D000465:Algorithms; D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003198:Computer Simulation; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D000077340:Fluvastatin; D016666:Fluvoxamine / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008024:Ligands; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013988:Ticlopidine / Q000378:metabolism
D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008024:Ligands; D000077340:Fluvastatin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D016666:Fluvoxamine; D013988:Ticlopidine