User Tools

Site Tools


chem331:molecular_docking_results

Molecular Docking Results

7,8-Dimethylalloxazine

Binding Affinity: -2.4 kcal/mol
7,8-Dimethylalloxazine

Analysis: The binding affinity of 7,8-Dimethylalloxazine is incredibly low for a desired inhibitor or activator. From the data collected in this experiment, 7,8-Dimethylalloxazine actually produced a promoter effect on growth. The location of interaction on FabG was actually different than those chemicals exhibiting inhibition effects on growth. Whether or not this is the reason for the chemical activity has not been explored.

7,8-Dimethylalloxazine bound to FabG

7,8-Dimethylalloxazine H-Bonding in binding pocket. RasMol Amino Acid Color Code
Figure 1. The image on the left illustrates just one example of the hydrogen bonding that occurs do to the interaction of 7,8-Dimethylalloxazine with the surrounding amino acid residues on FabG.

The interaction of the surrounding amino acids can be further analyzed using the RasMol Color Code of amino acids.

2-(3-hydroxyphenyl)-6,7-dimethyl-2H,4H-furo[2,3-b]quinoxalin-3-ol

by Michael McCormack

Binding Affinity: -6.0 kcal/mol

Interpretation: with a relatively low binding affinity, this molecule would probably not represent a potential target for the development of a novel antibiotic.

2D Structure of the Potential FabG Inhibitor

Figure 1

Potential Docking Position for the Inhibitor in FabG Molecule

Figure 2

Figure 2

The green molecule is the potential inhibitor. The FabG enzyme is color coded with red as oxygen, grey as carbon, purple as phosphorus, yellow as sulfur, and white as hydrogen.

Figure 3

Figure 3

Figure 3 shows a close up of where the potential inhibitor could be interacting with the FabG enzyme. The secondary structure (beta sheets and alpha helices) are colored in blue. The rest of the FabG enzyme as well as the potential inhibitor are color coded with red as oxygen, grey as carbon, purple as phosphorus, yellow as sulfur, and white as hydrogen.

Figure 4

Figure 4

Figure 4 shows a close up of where the potential inhibitor could be interacting with the FabG enzyme from a different angle. The FabG enzyme is color coded by amino acids according the rasmol color scheme and the potential inhibitor is colored according to the same scheme as in Figure 3.

Syringil

Syringil

Syringil Structure

Light blue- FabG structure

Red, Green, Yellow, Pink & Dark Blue- Conformations of Syringil

Binding affinity: -4.4 kcal/mol

Interpretation: Because the binding affinity is relatively low, at 4.4 kcal/mol, it is unlikely that this is a very specific inhibitor for fabG.

C11H9NO

by Jess Coulter

The compound shown above was also tested in the bioassay plate 4729. It has a similar structure to the two possible fabG inhibitors found in that plate (see bioassay results). This compound, C11H9NO, has a binding affinity -4.7 kcal/mol calculated by the Vina Autodock software. This docking experiment is shown below.

Within the bioassay it showed little promise as an antibacterial compound but with very slight (not statistically significant) fabG inhibitory capability. Compared to the two fabG inhibiting compounds, Benzo[c]cinnoline, N-oxide and C12H10N2S, of the bioassay plate 4729, it also sits in a the same active site. It has slightly less binding affinity than Benzo[c]cinnoline, N-oxide but practically the same binding affinity as C12H10N2S. This agrees with the bioassay results since Benzo[c]cinnoline, N-oxide showed more inhibitory power than C12H10N2S.

Benzo[c]cinnoline, N-oxide

by Daniel Rossie

Orange - FabG Structure

Green - NADP+ in active site

Blue - Highest affinity conformation of Benzocinnoline docked to the FabG protein

Binding affinity: -6.1 kcal/mol

Interpretation: The binding affinity is not high enough to be a FabG specific inhibitor due to its weak interactions with the protein.

C12H10N2S

C12H10N2S

C12H10N2S docked in fabGC12H10N2S docked in fabGC12H10N2S docked in fabG

White - FabG Structure

Green - Highest affinity conformation of C12H10N2S docked to the FabG protein

Binding affinity: -4.4 kcal/mol

Interpretation: At 4.4 kcal/mol, the binding affinity is not high enough to be a FabG specific inhibitor due to its weak interactions with the protein.

6-bromo-N-naphthalen-1-yl-1,3-benzodioxole-5-carboxamide

By Sariely Sandoval

6-bromo-n-naphthalen-1-yl-1_3-benzodioxole-5-carboxamide_and_fabg.jpg6-bromo-n-naphthalen-1-yl-1_3-benzodioxole-5-carboxamide_and_fabg_close_up.jpg

Red: Oxygen

Red Dots: Water

Grey: Carbon

Yellow: Sulfur

Purple: Phosphorous

White: Hydrogen

Blue: Secondary Structure of fabG

Green: Highest affinity conformation of 6-bromo-N-naphthalen-1-yl-1,3-benzodioxole-5-carboxamide docked to the FabG protein.

Binding affinity: -5.1 kcal/mol

Interpretation: Because the binding affinity is relatively low, 5.1 kcal/mol, it is unlikely that this is a specific inhibitor for fabG.

Beta-lapachone



Binding affinity: -5.3 kcal/mol
Interpretation: Because the binding affinity is relatively low, 5.1 kcal/mol, it is unlikely that this is a specific inhibitor for fabG.

Potential Docking


Figure 1.1. Potential Docking of beta-lapachone (Quaternary Structure).


Figure 1.2. Potential Docking of beta-lapachone (Primary Structure).


In figure 1.1, beta-lapachone can be seen filling the active site. The active site is more easily seen in figure 1.2. The colors of the FabG protein depicted in figure 1.1 correspond to its amino acid residues. These colors follow the rasmol amino acid code, which is shown below.
RasMol Amino Acid Color Code

Figure 2. Various angles of a possible docking position for beta-lapachone.


In figure 2, the quaternary structure of FabG is shown and colored according to the amino acid residues. The structure of beta-lapachone is shown in the most probable docking position. From this figure, possible interactions between beta-lapachone and its active site were determined.

Interactions

To better understand the low binding affinity of beta-lapachone to the FabG protein, possible interactions were analyzed using AutoDock software. Three possible interactions of beta-lapachone with its surrounding amino acids were found. These interactions are shown in figures 3, 4, & 5.

Figure 3. Possible interaction of ketone with active site. Figure 4. Possible interaction of ketone with active site. Figure 5. Possible interaction of ether with active site.


However, these are extremely weak interactions, and therefore, beta-lapachone has a low binding affinity.

chem331/molecular_docking_results.txt · Last modified: 2016/06/07 09:53 (external edit)