AutoDock 4 and AutoDock Vina -Brief Intruction Guanglin Kuang 2014-3-25

Docking -wikipedia General definition: In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using for example scoring functions. Usage: Docking is frequently used to predict the binding orientation of small molecule drug candidates to their protein targets in order to in turn predict the affinity and activity of the small molecule. Hence docking plays an important role in the rational design of drugs, for example, hit identification and lead optimization. lock-and-key

Theoretical Background Docking approaches: Shape complementarity Simulation Search algorithm: Systematic or Stochastic torsional searches about rotatable bonds Genetic algorithms to "evolve" new low energy conformations Molecular dynamics simulations Structural flexibility: Ligand flexibility Receptor flexibility (Induced fit docking) Scoring function: Force field Empirical Knowledge -based Popular Softwares: DOCK, AUTODOCK, GOLD, Glide (Schrödinger), FlexX (Sybyl), MOE-Dock … J. Med. Chem., 2004, 47 (12), pp 3032–3047 Nat Rev Drug Discov. 2004 Nov;3(11):935-49.

AutoDock 4.0 AutoDock is an automated procedure for predicting the interaction of ligands with biomacromolecular targets. The current version of AutoDock, using the Lamarckian Genetic Algorithm and empirical free energy scoring function. AutoDock calculations are performed in several steps: Preparation of coordinate files using AutoDockTools Recalculation of atomic affinities using AutoGrid Docking of ligands using AutoDock, Analysis of results using AutoDockTools. Journal of Computational Chemistry, Vol. 19, No. 14, 1639]1662 (1998) Journal of Computational Chemistry: Volume 30, Issue 16, pages 2785–2791, December 2009 http://autodock.scripps.edu/

AutoDock Vina Advantages (Compared to AutoDock 4.0): Disadvantages AutoDock 4 and AutoDock Vina were both developed in the Molecular Graphics Lab at The Scripps Research Institute. AutoDock Vina inherits some of the ideas and approaches of AutoDock 4 . They use the same type of structure format (PDBQT) for maximum compatibility with auxiliary software. However, the source code, the scoring function and the actual algorithms used are brand new. Advantages (Compared to AutoDock 4.0): Faster (can be used for virtual screening) Ease of use More accurate (arguably) Disadvantages The algorithm and scoring function is not as straightforward and physical as that of AutoDock 4. Works more like a black-box Journal of Computational Chemistry, Volume 31, Issue 2, pages 455–461, 30 January 2010 http://vina.scripps.edu/manual.html

Virtual Screening Using Vina Step 1: Prepare the protein: Use AutoDockTools Step 2: Prepare the Ligands: Step 3: Virtual Screening Step 4: Analysis Find the top scored ligands: vina_screen_get_top.py Analyze the binding modes with AutoDockTools corina -d wh,rs,neu,r2d,errorfile=errors.sdf database.sdf database-3D.sdf babel -isdf database-3D -opdb ligand.pdb -m #! /bin/bash for f in ligand*.pdb; do b=`basename $f .pdb` echo Processing ligand $b mkdir -p $b pythonsh $ADT_Utilities24/prepare_ligand4.py -l $f -o ${b}/${b}.pdbqt done conf.txt receptor = protein.pdbqt cpu = 8 center_x = -2.0 center_y = 57.1 center_z = 52.3 size_x = 22.5 size_y = 22.5 size_z = 22.5 #! /bin/bash for f in ligand*.pdb; do b=`basename $f .pdb` echo Processing ligand $b vina --config conf.txt --ligand ${b}/${b}.pdbqt --out ${b}/${b}_out.pdbqt --log ${b}/${b}_log.txt done http://vina.scripps.edu/manual.html

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