COMP 253 |
| A lot of modern methods for virtual discovery predicts a bioactivity at the stage of receptor – ligand interaction. At the same time a biological action of a drug includes more than one stage of action even in cases of in vitro experiments. Therefore, a new method for virtual discovery is proposed. The method creates pseudo-atomic receptor model and allows to simulate a movement of a drug molecule to the receptor through water and membrane. The interaction with competitive sites is taken into account. Also the method allows to presuppose a metabolism of drug. The method has been used for detailed elucidation of stages of action for membranotropic dihydrofolatereductase inhibitors. It has been shown that the process of biological action of the drugs includes 3 critical stages: penetration through membrane, diffusion and interaction with the target. Some of compounds play a role of pro-drugs and their metabolism yields to an active molecule. The quantitative relationships for each of the stages are obtained. The importance of every stage is estimated for each molecule. Now the algorithm is used for virtual screening of more than 20 kinds of biological activities.
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Phil Magee Memorial Symposium: QSAR Reborn
1:30 PM-4:50 PM, Tuesday, August 21, 2007 BCEC -- 156C, Oral
Division of Computers in Chemistry |