Peter Kolb, Marco Cecchini, Danzhi Huang,
pkolb, cecchini, majeux, dhuang, [email protected]
Department of Biochemistry, University of Zurich, Switzerland
Our approach consists of four modules (I
), which perform
FFLD  uses a Genetic Algorithm to dock the whole – fully
different steps of the docking procedure.
flexible – molecules by trying to place the fragments identified
by DAIM at the positions determined by SEED–SFI. The scoringfunction contains terms for van-der-Waals interaction, hydrogen
DAIM preprocesses the molecules and decomposes them into
bonds and unfavorable polar contacts.
chemical fragments. It also allows to filter the molecules for theoccurence of certain fragments to reduce the library size.
FFLD generates a conformation and tries to put it on the corresponding
Validation on HIV-1 Protease
molecule with the fragments identified by DAIM.
A set of 4 different HIV-1 protease–ligand complexes was usedto test the docking approach. The number of ligand rotatablebonds (corresponding to the number of degrees of freedom, sincethe protein is kept rigid) ranged from 10 to 22. All ligands could
SEED [1, 2] places the rigid fragments in the binding site us-
ing an accurate energy function including electrostatic solvation
based on the generalized Born approach . The electrostaticcomponent of the binding energy is approximated by the sum ofthe following terms:
Screened receptor-fragment interaction: intermolecularelectrostatic energy between the fragment and the receptorin the solvent.
Partial desolvation of the receptor (fragment): electro-
Structure of an HIV-1 protease inhibitor with 21 rotatable bonds docked
static energy difference caused by the displacement of
by FFLD (thick, yellow). The X-ray structure (thin, green) is shown as
high dielectric solvent by the volume of the fragment (re-
a basis of comparison. RMSD (heavy atoms) 1.05 ˚
Application on -Secretase (Alzheimer)
We have recently screened a library of 10’000 compounds (with2-11 rotatable bonds) for
SFI clusters the geometrical centers found by SEED to re-
MAJEUX, N., SCARSI, M., APOSTOLAKIS, J., EHRHARDT, C., AND CAFLISCH, A. Exhaustive docking of molec-ular fragments with electrostatic solvation. Proteins 37
MAJEUX, N., SCARSI, M., AND CAFLISCH, A. Efficient electrostatic solvation model for protein-fragment dock-ing. Proteins 42
SCARSI, M., APOSTOLAKIS, A., AND CAFLISCH A. Continuum Electrostatic Energies of Macromolecules inAqueous Solutions. J. Phys. Chem. A 101
BUDIN, N., MAJEUX, N., AND CAFLISCH, A. Fragment-based flexible ligand docking by evolutionary optimiza-tion. Biol. Chem. 382
Selective Serotonin Reuptake Inhibitors and Selective serotonin reuptake inhibitors Prozac, Prozac Weekly, and Sarafem (fluoxetine) Mixed-action antidepressants Pristiq (desvenlafaxine)Remeron (mirtazapine)Wellbutrin, Wellbutrin SR, and Wellbutrin XL (bupropion)The antidepressants known as selective serotonin reuptake inhibitors (SSRIs) have become widely used to treat major depressio
MATERIAL SAFETY DATA SHEET DRAGNET® SFR TERMITICIDE/INSECTICIDE MSDS Ref. No.: 52645-53-1-26 Date Approved: 02/29/2008 Revision No.: 11 This document has been prepared to meet the requirements of the U.S. OSHA Hazard Communication Standard, 29 CFR 1910.1200 and Canada’s Workplace Hazardous Materials Information System (WHMIS) requirements. 1. PRODUCT AND COMPANY ID