Download Molecular Modeling

Alex Strube
Molecular Modeling
Alex Strube
In this assignment, I downloaded a model of a protein-heterocompound complex involving
aspirin as the heterocompound, in .pdb format, from RCSB PDB, a protein database. I extracted
the model of the complexed aspirin from the larger model of the complex using DS Visualizer
software. It is displayed as Figure 1.
Fig. 1: Ball and Stick model of aspirin (AIN)
Figure 2 is a Lewis structure of aspirin drawn by me using ChemSketch software. It includes free
pairs of electrons.
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Alex Strube
Fig. 2: Lewis structure of aspirin (AIN)
Figure 3 is the complex, with the protein part displayed as solid ribbons. The oxygens in the
heterocompound are red.
Fig. 3: Complex formed between group II phospholipase A2 (1tgm) and aspirin (AIN).
PART 2
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Alex Strube
Steric Energy
Type
Stretch:
Bend:
Stretch-Bend:
Torsion:
Non-1,4 VDW:
1,4 VDW:
Charge/Charge:
Charge/Dipole:
Dipole/Dipole:
Total Energy:
Before Minimization (kJ/mol)
Aspirin
After Minimization (kJ/mol)
10.2188
0.7243
13.6498
2.269
1.2804
0.1125
-1.8859
-4.0479
-0.6237
0.1748
5.4816
7.1752
0
0
-3.2548
-3.4975
5.0818
5.1659
29.9479
8.0763
Table 1: single-point energy calculation on the extracted heterocompound and energy minimization
Fig.4: Aspirin in the conformation in which it complexes with 1tgm.
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Alex Strube
Fig. 5: Energy minimized aspirin conformation.
Table shows steric energy values for aspirin in the conformation in which it complexes with
1tgm compared to its minimum energy conformation. The value for total steric energy for the
original conformation was 29.9479 kJ/mol; The value for total steric energy for the minimized
conformation was 8.0763 kJ/mol. For stretch energy, which represents the energy associated with
any bonds that are distorted from their optimal length, the value for the original conformation
was higher than the value for the minimized conformation. For bend energy, which represents
the energy associated with any bond angles that are deformed from their optimal values, the value
for the original conformation was higher than the value for the minimized conformation. For
stretch-bend energy, which represents the energy required to stretch the two bonds involved in a
bond angle when that bond angle is severely compressed, the value for the original conformation
was higher than the value for the minimized conformation. For torsion energy, which represents
the energy associated with deforming torsional angles (dihedral angles) in the molecule from their
ideal values, the value for the original conformation was higher than the value for the minimized
conformation was. For Non-1, 4 van der Waals energy, which represents the energy for the
through-space interaction between pairs of atoms that are separated by more than three atoms,
the value for the original conformation was lower than the value for the minimized
conformation was. For 1, 4 van der Waals energy, which represents the energy for the throughspace (non-bonded) interaction of atoms separated by two atoms, the value for the original
conformation was lower than the value for the minimized conformation was. For dipole/dipole
energy, which represents the energy associated with the interaction of bond dipoles, the value for
the original conformation was lower than the value for the minimized conformation was.
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Alex Strube
Fig. 6: The original heterocompound conformation superimposed with the energy minimized
conformation.
The original heterocompound conformation was superimposed with the energy minimized
conformation using the overlay function of Chem3D Ultra. Use this function by going to View |
Model Explorer: A pane identifying the each molecule in the active window as fragments will
open. Choose one fragment using Structure | Overlay | Set Target Fragment. Select the other
fragment and choose Structure | Overlay | Fast Overlay. The molecules will be superimposed.
Except for a few hydrogen atoms, the atoms of the two conformations all partially overlap.
Perhaps this means the original conformation was already at a low energy.
PART 3
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Alex Strube
Fig. 7: Primary structure of 1tgm.
Fig. 8: Ligplot for AIN.
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Alex Strube
Fig.8: Ligand Interactions with Certain Amino Acids on 1tgm.
Fig.9: Ribbon Model of 1tgm Showing Legend Interactions with Certain Amino Acids on 1tgm.
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Alex Strube
Figure 7 shows the primary structure of Phospholipase A2, also known by the PDB ID: 1tgm.
Each letter represents an amino acid; the red dots over some letters indicate ligand interactions.
Figures 8, 9, and 10 show the interaction between aspirin and three amino acid residues, Leu 2,
Ala 18, and Ile 19, in the Phospholipase A2 protein. Figure 8 is a LigPlot. The “eyelashes” in
figure 8 indicate hydrophobic interactions between these amino acid residues in the protein
and the heterocompound aspirin.
PART 4
Amino acid residue & position # Atoms in hetero that interact
!interaction
LEU 2
C8 & C9
hydrophobic
ALA 18
C4, C3, C7, O1 & O2
hydrophobic
ILE 19
C4, C3, C7, O1 & O2
hydrophobic
Table 2: Amino Acid Residue Interactions.
Table 2 lists the amino acid residues in 1tgm that interact with the complexed
heterocompound aspirin, their positions in the protein’s primary structure, which atoms they
interact with in the heterocompound, and what type of interaction (hydrogen bond or
hydrophobic) the LigPlot indicates.
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Alex Strube
References:
1. RCSB. “1tgm.” RCSB PDB: Structure Explorer. Dec. 2, 2008.
http://www.rcsb.org/pdb/explore/explore.do?structureId=1TGM
2.Singh, N., Jabeen, T., Sharma, S., Bhushan, A., Singh, T.P. Crystal structure of a complex formed
between group II phospholipase A2 and aspirin at 1.86 A resolution To be Published. Similar
published article link: http://www.ebi.ac.uk/thornton-srv/databases/cgibin/pdbsum/GetPage.pl?pdbcode=2pws&template=main.html.
3. PDBSum. “Ligand/Metal Interactions: 1tgm.” http://www.ebi.ac.uk/thornton-srv/databases/cgibin/pdbsum/GetPage.pl?pdbcode=1tgm&template=ligands.html&l=1.1
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