Improving Binding Energy using Quantum Mechanics

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Improving Binding Energy using Quantum Mechanics

• Michelle Di Fiore
• Melbourne, Australia
• Monash University
• August 17, 2007

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Proposed Research

• Using Quantum Mechanic methods in GAMESS and
  classical electrostatic methods in APBS, I will
  estimate the binding energy between proteins and
  ligands. To improve the binding energy, the
  orientation of the phenyl rings in the binding
  site will be changed by 30 degrees and new
  calculations will be made.

• Rotation of the indole ring of the Substituted
  tryptophan
• Rotation of the phenyl ring of the Phenylalanine
  69
• Rotation of the phenyl ring of PHE64

See the influence of the orientation of the ring
gt aromatic networks in the binding site
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Research Goals

• Construct a computational pipeline for high
  throughput molecular modeling using GAMESS, APBS,
  or GAMESS/APBS hybrid.
• GAMESS will be used for smaller molecules,
  including the ligand component of a protein
  system
• APBS is used for the larger biological
  components, for computation of electrostatic
  interactions and effect of environment, using the
  Poisson-Boltzmann equation.
• GAMESS/APBS hybrid method is used to estimate the
  binding energy between ligand and protein in a
  complex environment.

These same computational methods and pipeline
could be reused for a large variety of
computational molecular modeling problems
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Progress

• Created input files to run a set of non-natural
  base pairs and sugars to find out more of the
  interaction between base pairs properties
  electrostatics of bases and base pairs
• These input files have started to be run on
  GAMESS on the Zurich site and at Monash.
• Set up a plan file the p53 complex that Celine
  and I are working on so we can run it through
  Nimrod/G and get the binding energies at the 30
  degree intervals.
• Installing QM view

Elmhurst College, Charles E Ophardt
thymine
adenine
Royal Society of Chemistry
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Next Week

• Finish running the input for GAMESS and use the
  results to start running the molecules through
  APBS
• Update the plan file so that it can work with
  different complexes
• Determine final results for the binding energy of
  the p53 complex binding with HDM2

Phenylalanine
6
Sovereign Hill
7
All around Melbourne