Introduction 5

Overview of the Method 6

Applications 7

What's New 9

Grid Maps 11

Van der Waals Potential Energy 12

Modeling Hydrogen Bonds 17

A note on atom type codes: 18

Electrostatic Potential Grid Maps 19

Getting Started... 21

Setting Up AutoGrid and AutoDock Jobs 22

Preparing the Ligand 23

Ligand Flexibility and Constraints 23

Using AutoTors to Define Torsions in the Ligand 25

Ligand is in PDBQ-format: 25

Ligand is in Mol2-format: 25

AutoTors Output: 25

AutoTors Flags: 26

Running AutoTors 26

Root Selection 27

Torsion Selection 27

Adding Polar Hydrogens to the Macromolecule 27

Running AutoGrid 28

Flexible Docking with AutoDock 28

Monte Carlo Simulated Annealing 30

Genetic Algorithm and Evolutionary Programming Docking 30

Running AutoDock 31

Using the Command Mode in AutoDock 32

Trajectory Files 34

Evaluating the Results of a Docking 36

Visualizing Grid Maps 37

Visualizing Trajectories 37

Appendices 38

Shell Scripts and Awk Programs 38

Parameters from AutoDock Version 1 48

AutoDock File Formats 49

PDBQ Format 49

PDBQS Format 49

AutoGrid Grid Parameter File (GPF) Format 50

AutoGrid Keywords 51

Grid Map Format 53

Grid Field Format 53

AutoDock Docking Parameter File (DPF) Format 53

Command to set the seed for the random number generator 54

Parameters defining the grid maps to be used 54

Parameters defining the ligand and its initial state 55

Parameters defining ligand step sizes 57

Parameters defining optional ligand torsion constraints 57

Parameter affecting torsional free energy 59

Parameters for ligand internal energies 59

Parameters for simulated annealing searches 60

Parameter to set the level of output 61

Parameters for trajectory output during dockings 62

Parameter for energies of atoms outside the grid 62

Parameter for initializing the ligand 63

Parameters for cluster analysis of docked conformations 63

Parameters for re-clustering the results of several jobs 64

Parameters for genetic algorithm and evolutionary programming searches 64

Command to set genetic algorithm parameters 65

Parameters for local search 66

Commands to choose and set the local search method 67

Commands to perform automated docking 67

Command to perform clustering of docked conformations 68

Example Parameter Files 69

AutoGrid 69

AutoDock 70

Example 1. Docking using Monte Carlo Simulated Annealing 70

Example 2. Clustering Conformations from Many Dockings 71

Example 3. Docking using the Genetic Algorithm plus pseudo-Solis & Wets 72

AutoDock References 74

Primary References 74

Applications of AutoDock 74

Web publications 76