AutoDock Results

Using the Simulated Annealing Search Engine

These animations show the docked conformations generated by 100 independent runs of AutoDock version 2.4. In each case, the crystallographic conformation is represented in green. Each atom of a docked conformation samples an intermolecular atomic affinity grid and a color is assigned to each atom based on the color range shown. Atoms with repulsive energies thus appear red, while those with attractive energies are blue. Hence the coloring changes depending on the conformation. The sampling method does not take into account the atom type: for example, if the ligand is sampling a carbon-affinity grid, hydrogen atoms are colored as if they were carbon atoms. Note that only polar hydrogens are explicitly treated; non-polar hydrogens are "unified" with their parent heavy atom, by increasing the heavy atom's van der Waals' radius.

The molecular surface of each protein was calculated using MSMS, Michel Sanner's molecular surface program. The MPEG movies were generated using AVS, with a version of the "Create_MPEG" module, modified for the 64-bit DEC Alpha platform. The original version of the Create_MPEG module came from the International AVS Center (IAC).

Final Docked Conformations

It is worth emphasizing here that each frame in these animations shows the result of a separate AutoDock run. Each of these runs began with the ligand in a completely random translation, random orientation and, where appropriate, random torsion. We are not seeing trajectories of the ligand during a docking (although this is possible with AutoDock).

The docked conformations are sorted in order of increasing energy, so the lowest energy docked conformation is the first frame in every movie. Note how well this corresponds with the crystallographic coordinates of the ligand.

Benzamidine binding to beta-Trypsin (3ptb)
691K MPEG.
Every atom of the ligand, benzamidine, is color coded by C-atom affinity. The blue color of the phenyl ring indicates that it has a favorable interaction energy in all the 100 dockings. Note the NH₂ groups are colored red; these atoms are also sampling the carbon affinity grid, even though they do not in the actual dockings: this is a limitation of the "sample" module in AVS. The crystallographic coordinates of benzamidine are shown in green.

Camphor binding to Cytochrome P-450 (2cpp)
1,585K MPEG.
The color coding is by carbon-atom affinity. The crystallographic coordinates of camphor are shown in green. Also shown are the heme moiety and Tyr-96, which donates a hydrogen bond to camphor. The backbone of cytochrome P-450cam is represented by ribbons, which was generated by an AVS module written by Alex Shah, around Mike Carson's Ribbons code. Note the slight unwinding of the proximal helix, I, which helps form the dioxygen binding pocket, to the right of this picture.

Phosphocholine binding to McPC-603 (2mcp)
1,077K MPEG.
Note the transparent bluish pockets of oxygen affinity, which is iso-contoured at -2.5 kcal/mol. The phosphocholine molecule is coloured by oxygen affinity, also. Compared to the camphor and benzamidine dockings, there is much wider spread of final docked conformations, although the lowest energy cluster is the one which corresponds most closely to the observed conformation, shown in green.

Biotin binding to Streptavidin (1stp)
884K MPEG.
This movie shows the ligand biotin and its final docked conformations after 100 AutoDock dockings to streptavidin. Like all the other movies on this page, the order of conformations in this animation is from lowest energy to highest. The crystal structure conformation of biotin is shown in green. Note the beautiful, elongated binding cleft. To give an idea of scale, the sides of the grid shown in the background are 22.875 Å long.

XK-263 inhibitor binding to HIV-1 Protease (1hvr)
899K MPEG.
Here we can see how a large inhibitor binds to HIV-1 protease. The inhibitor in question is a Merck-Dupont compound, XK-263, which consists of a 7-membered cyclic urea moiety (viewed edge-on in the picture to the right), with phenyl and naphthyl rings branching off on either side. The cyclic carbonyl-oxygen mimics water-301, which is structurally conserved in the apo-form of the enzyme, but is displaced by this functionality in the complex. The lower part of the cyclic urea has two adjacent hydroxyls that H-bond to the catalytic aspartates. Note that there are a large number of docked conformations which do not gain access to the tunnel of the active site, but instead find higher energy local minima near the entrances. The crystal structure of the complexed protease inhibitor, XK-263, is shown in green. The protease is represented by a ribbon diagram: the two flaps run diagonally from upper left to lower right.

Sialic acid binding to Hemagglutinin (4hmg)
973K MPEG.
The binding of sialic acid to a pocket of conserved amino acids in influenza virus hemagglutinin docking is dominated by hydrogen bonding. Sialic acid has 5 hydroxyls, 1 carboxylate, a cyclic ether oxygen, and an acetamido group, along with 10 rotatable bonds. While there are several possible ways of matching these hydrogen bonding functional groups with the corresponding regions of affinity in the protein, only one mode is observed in the crystal structure. Out of 100 dockings, the lowest energy found had an rmsd from the crystal structure of 1.40 Å. This lowest cluster had 5 members, with the lowest rmsd from the crystal being 1.27 Å.

AutoDock

Movies

Benzamidine binding to beta-Trypsin (3ptb) 691K MPEG. Every atom of the ligand, benzamidine, is color coded by C-atom affinity. The blue color of the phenyl ring indicates that it has a favorable interaction energy in all the 100 dockings. Note the NH₂ groups are colored red; these atoms are also sampling the carbon affinity grid, even though they do not in the actual dockings: this is a limitation of the "sample" module in AVS. The crystallographic coordinates of benzamidine are shown in green.
Camphor binding to Cytochrome P-450 (2cpp) 1,585K MPEG. The color coding is by carbon-atom affinity. The crystallographic coordinates of camphor are shown in green. Also shown are the heme moiety and Tyr-96, which donates a hydrogen bond to camphor. The backbone of cytochrome P-450cam is represented by ribbons, which was generated by an AVS module written by Alex Shah, around Mike Carson's Ribbons code. Note the slight unwinding of the proximal helix, I, which helps form the dioxygen binding pocket, to the right of this picture.
Phosphocholine binding to McPC-603 (2mcp) 1,077K MPEG. Note the transparent bluish pockets of oxygen affinity, which is iso-contoured at -2.5 kcal/mol. The phosphocholine molecule is coloured by oxygen affinity, also. Compared to the camphor and benzamidine dockings, there is much wider spread of final docked conformations, although the lowest energy cluster is the one which corresponds most closely to the observed conformation, shown in green.
Biotin binding to Streptavidin (1stp) 884K MPEG. This movie shows the ligand biotin and its final docked conformations after 100 AutoDock dockings to streptavidin. Like all the other movies on this page, the order of conformations in this animation is from lowest energy to highest. The crystal structure conformation of biotin is shown in green. Note the beautiful, elongated binding cleft. To give an idea of scale, the sides of the grid shown in the background are 22.875 Å long.
XK-263 inhibitor binding to HIV-1 Protease (1hvr) 899K MPEG. Here we can see how a large inhibitor binds to HIV-1 protease. The inhibitor in question is a Merck-Dupont compound, XK-263, which consists of a 7-membered cyclic urea moiety (viewed edge-on in the picture to the right), with phenyl and naphthyl rings branching off on either side. The cyclic carbonyl-oxygen mimics water-301, which is structurally conserved in the apo-form of the enzyme, but is displaced by this functionality in the complex. The lower part of the cyclic urea has two adjacent hydroxyls that H-bond to the catalytic aspartates. Note that there are a large number of docked conformations which do not gain access to the tunnel of the active site, but instead find higher energy local minima near the entrances. The crystal structure of the complexed protease inhibitor, XK-263, is shown in green. The protease is represented by a ribbon diagram: the two flaps run diagonally from upper left to lower right.
Sialic acid binding to Hemagglutinin (4hmg) 973K MPEG. The binding of sialic acid to a pocket of conserved amino acids in influenza virus hemagglutinin docking is dominated by hydrogen bonding. Sialic acid has 5 hydroxyls, 1 carboxylate, a cyclic ether oxygen, and an acetamido group, along with 10 rotatable bonds. While there are several possible ways of matching these hydrogen bonding functional groups with the corresponding regions of affinity in the protein, only one mode is observed in the crystal structure. Out of 100 dockings, the lowest energy found had an rmsd from the crystal structure of 1.40 Å. This lowest cluster had 5 members, with the lowest rmsd from the crystal being 1.27 Å.