Universiti Sains Malaysia

1
Universiti Sains Malaysia
Ranmali Perera

August 15, 2008
Comparison of AutoDock and GAMESS/APBS Methods
for Performing Molecular Computations on
Biological Systems
2
Proposed Research

• The enhancement of previously designed framework
  for ligand-protein investigations using
  GAMESS/APBS tools
• Comparison of data obtained from AutoDock and
  GAMESS/APBS
• Find ligands that bind to HDM2 and give the
  lowest free energy of binding values
• HDM2 binds to the tumor suppressor protein p53.
  My goal is to find a ligand that binds to HDM2,
  and thus inhibits HDM2 from binding to p53.
• Visualization, analysis, and archival of results
• NIMROD will be used for this workflow

3
Progress

• Created 100 GAMESS output files
• Ran APBS for 80 ligands (for the solvation energy
  contribution to binding)
• Control docking for the beta-hairpin (including
  6ClW) and HDM2
• Docked 1990 NCI Diversity Set ligands to HDM2
  using AutoDock and GridSphere used two different
  grid centers
• Recorded which ligands gave the lowest free
  energy of binding to HDM2 (for the AutoDock
  method)
• Visualized these ligands to see where they are
  located in the active site/deep cleft of HDM2

4
Goals for the Future

• Run APBS on ligands to find apolar contribution
  to binding energy
• Analyze results for GAMESS/APBS and AutoDock
• See which method gives lower binding energy
  values
• Find similar substituents among the ligands that
  give the lowest free energy of binding

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As the end of the internship approaches

• Finish running GAMESS and APBS
• Do one more docking using AutoDock and GridSphere
• Start analysis of data
• Back-up and document all data
• Find a way to take data files back home with me
• Say Goodbye to everyone in the lab ?

6
Batu Ferringhi Beach
Reading The Star newspapers report on the
Olympics
Happy graduate and her proud parents
Congratulations Yeesiew!
7
Making friends with a butterfly!
At the Penang Butterfly Farm
Posing with the bride and groom
A Malay Wedding