title: Computational insights into the inhibition of inosine 5'-monophosphate dehydrogenase by mycophenolic acid analogs: three-dimensional quantitative structure-activity relationship and molecular docking studies.
abstract: Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo synthesis of guanosine nucleotides. It is considered as an important target in the quest for drugs in the immunosuppressive, antiviral, antibacterial, and anticancer therapeutic areas. Herein, we report the 3D-QSAR analyses using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking on mycophenolic acid derivates for the first time. We obtained cross-validated q(2)  value of 0.805 for CoMFA and 0.620 for CoMSIA, while the non-cross-validated r(2)  values for them were 0.969 and 0.935, respectively. Based on the CoMFA and CoMSIA contour maps and docking analyses, some key structural factors responsible for inhibitory activity were revealed. The results obtained from this study could be used for the rational design of potent inhibitors against IMPDH.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.forename: Qing-He
authors.initials: QH
authors.lastname: Wang
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Yang
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Mao-Sheng
authors.initials: MS
authors.lastname: Cheng
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016018:Least-Squares Analysis; D009173:Mycophenolic Acid / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid