کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
691741 1460449 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Drug design for mPGES-1 from traditional Chinese medicine database: A screening, docking, QSAR, molecular dynamics, and pharmacophore mapping study
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی تکنولوژی و شیمی فرآیندی
پیش نمایش صفحه اول مقاله
Drug design for mPGES-1 from traditional Chinese medicine database: A screening, docking, QSAR, molecular dynamics, and pharmacophore mapping study
چکیده انگلیسی
To search for new anti-inflammatory that can replace the current COX-1 and COX-2 inhibitors, virtual screening by molecular docking of traditional Chinese medicine (TCM) molecules into microsomal prostaglandin E2 synthase (mPGES-1) glutathione binding site was performed. To compare the top ranking derivatives with other mPGES-1 inhibitors, we constructed QSAR models using comparative molecular force field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA model had a non-cross-validated coefficient (r2) and a cross-validated coefficient (q2) of 0.960 and 0.597. The r2 and q2 for CoMSIA (S + H + D) was 0.931 and 0.719, respectively. The top three TCM derivatives all can map into the respective steric, hydrophobic and hydrogen bond donor force fields. The top ranking TCM molecules were taken for de novo design; the top three de novo products were further analyzed using molecular dynamics simulation and qualitative structure-activity relationship (QSAR) model. Derivative, 2-O-caffeoyl tartaric acid-Evo_2, glucogallin-Evo_1 and 4-O-feruloylquinic acid-Evo_7, all had conserved hydrogen bond networks to key residues Arg38 and Arg70 during the 20 ns molecular dynamics simulation. In addition, all derivative-protein complexes had total energy lower the control-protein complex. Combining the results from molecular dynamics simulation and CoMFA/CoMSIA, we suggest 2-O-caffeoyl tartaric acid-Evo_2, glucogallin-Evo_1 and 4-O-feruloylquinic acid-Evo_7 as potent mPGES-1 inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the Taiwan Institute of Chemical Engineers - Volume 42, Issue 4, July 2011, Pages 580-591
نویسندگان
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