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B.Preparing Ligand
1. Open wordpad Type script based on page 37 of lab manual and x=16, y=25
and z=4 [center_x,y,z]and size_x,y,z as 30Save file as indinavir.txt.
For Nelfinavir:
The crystal binding mode wasnt reproduced actually the major difference as in
question 1 is around C33-36. Also to be noted indinavir has 14 active torsions. We
also know indinavir has 12 rotatable bonds. Theoretically, the more rotatable bonds
in the ligand, the more difficult it will be to find good binding modes in repeated
docking experiments. This is why there is a difference in structure.
The docking accuracy was evaluated in terms of the root mean square deviation
(RMSD) between the docked position and the experimentally determined position
for the ligand. The energy scores of the conformers were then merged for each
ligand. A total of 9 modes obtained. The conformer with the lowest score
represented the best docked ligand that is the mode 1 with affinity of -11.5kcal/mol,
and rmsd of 0 .
3. Perform molecular docking of nelfinavir into HIV-1 protease. Based on
indinavir docking, dock nelfinavir into HIV-1 protease and discuss your
results?
The score for the best conformer of nelvinavir is -10.1kcal/mol at 0 rmsd which is
actually more negative than indinavir. Making indinavir a better protease inhibitor
since it has lower energy thus it is more stable. Besides, Nelfinavir has 12 active
torsions based on our results log file. It has rotatable bond count of 10. Making this
less flexible than indinavir. We also see that only the docked structure can binds to
the structure rather than the original ligand. Also all the docked structures vary from
the original ligand if compared to nelfinavir at least had one slightly similar
structure.
Conclusions:
1. Docking results in a few crucial files namely Log file which is a log file describing
the tasks performed and noting any warnings or errors. A DockedLigand.pdb file
that has the best (i.e. lowest docking scores) poses of the docked ligand in PDB
format. Also a DockedLigand.log file containing the Vina docking scores for these
best poses. Hereby, poses with similar docking scores should be treated as equally
likely. As well as a ligand.pdbqt file having the target ligand in PDBQT format.
2. PDBQT is a file type which stores the atomic coordinates, partial charges and
AutoDock atom types, for both the receptor and the ligand.
References:
1. http://en.wikipedia.org/wiki/Macromolecular_docking
2.
http://graylab.jhu.edu/pyrosetta/downloads/documentation/Workshop7_PyRosetta_D
ocking.pdf
3. http://autodock.scripps.edu/faqs-help/tutorial/using-autodock-with-
autodocktools/UsingAutoDockWithADT_v2e.pdf
4. http://ashujo.wordpress.com/2007/05/05/how-do-you-choose-a-good-crystal-
structure-for-docking/
5. http://docking.utmb.edu/faq.php