Molecular dynamics simulations, Docking, Quantum chemistry calculation, Pharmacophore analysis

計畫名稱:Molecular dynamics simulations, Docking, Quantum chemistry calculation, Pharmacophore analysis

所屬單位:藥學系

研究團隊:生物資訊實驗室

計畫主持人:林榮信

研究人員:王瑞智

資源需求:Amber, Gaussian, g++, ifort, LAPACK, IMSL, Catalyst, Sybyl

使用期間:2006/05~

研究主題:
Molecular dynamics simulations, Docking, Quantum chemistry calculation, Pharmacophore analysis

研究內容概述:
Recognizing the fact that many novel drugs failed to pass clinical evaluation is mainly due to their poor ADME/T properties, the recent focus of our lab has been developing an integrated computational methodology that can help predict the ADME/T properties of new candidate compounds in the early phases of drug development. The first part of this integrated methodol-ogy includes identification of substrates or inhibitors of metabolic enzymes, e.g., cytochrome P450 and the efflux pump, e.g., P-glycoprotein, which will facilitate homology modeling, dock-ing, and molecular dynamics simulations, and binding free energy calculations. The second part will include QSAR prediction of intestinal permeability, blood brain barrier, among other impor-tant ADME/T properties based on passive transport mechanism. In the past, we have proposed the "relaxed complex" scheme that can accommodate receptor flexibility for structure-based drug design, and it has been demonstrated that this computational approach can reach the same accu-racy as the "SAR by NMR" method for lead optimization. Along the same line we will continue to explore the significance of protein flexibility for molecular recognition.Besides the develop-ment of new computational methodology, we have also been developing new antitumor agents based on virtual screening of large chemical databases. The current approach is to design a potent inhibitor to block the function of farnesyltransferase, which plays a very important role for the post-translational modification of the Ras protein.

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