Protein CAD Model

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Protein CAD Model

• Matthew M F Yuen
• Hong Kong University
• of Science and Technology
• Hangzhou September 13, 2003

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Features

• Molecular builder
• Atom builder allow for adding and modifying
  single atoms and bonds.
• Protein chain constructor can build and alter
  short polypeptides.
• Computational engine
• Superpositioning algorithm
• Structural alignment of protein chains.
• Protein chain refinement algorithm. Uses a set of
  heuristic rules to reconstruct and refine the
  polypeptide chain.

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Features

• General
• Real time monitoring of various molecular
  properties, including distances, angles (bond,
  torsional and improper), coordinate and distance
  RMS deviations.
• Graphical features
• Various styles of visualization (wire, cylinders,
  VdW spheres, ball-and-stick, polygon, ribbon,
  strands, tube, string, cartoon). Possible using
  several rendering styles in a single picture.
• Output to bitmap and PostScript formats.
  Generating ray-traced images using external
  software (POV-Ray).
• Animation of simulation trajectories. Capability
  of interpolating of consecutive frames, so high
  frequency molecular motion can be filtered out.

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Example - Aspirin
Aspirin
Stick model
Ball stick model
CPK model
Aspirin - optimized
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Example Procolipase
Hydrogen-free structure - line model
Hydrogen-free structure ribbon/tube model
Porcine pancreatic procolipase from Brookhaven
Protein Data Bank as determined by NMR
Spectroscopy
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Examples

Heme molecule complexed with Fe and Cl-.
Balls-and-sticks combined with VdW-spheres.
Fullerene nanotube (perspective view, capped
cylinders colored by atom order).
Two 434 CRO protein molecules (solid ribbon)
complexed with a piece of DNA double helix
(wireframe), pdb3cro.
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Examples

Crambin (pdb1crn) tube model with cysteines
displayed as balls-and-sticks.
1,25a-dihydroxyvitamin D complexed with its
receptor protein (glass tube colored by secondary
structure, contacting amino acids as capped
cylinders, and ligand molecule as CPK-colored
balls-and-sticks).
THE ABOVE INFORMATION COMES FROM
BIODESIGNER http//www.pirx.com/biodesigner/inde
x.shtml
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Potential Energy - Ethane

• Ethane composed of two rigid CH3 fragments joined
  by C atoms but are free to rotate about the
  internuclear C-C axis. There are three identical
  minima separated by 120?

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Protein Docking
Niacin
Vitamin C

• Interaction between Niacin and Vitamin C. Amino
  acid interact with each other to approach
  equilibrium

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Molecular Mechanics
Potential Energy Surface
Bonding Model
MM
Experimental Data
QM
Conventional Method
Alternative Method

• The alternative development in recent years is to
  use empirical models, based on experimental data,
  to calculate potential energy surfaces, and
  molecular mechanics is the least computational
  intensive method that is able to compute energy
  and structural information.

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Potential Energy Functions
Total strain energy
Ed Eb E? E? E? Eb two body bonding
energy E? three body valence angle energy E?
four body interaction torsional energy E?
four body interaction out-of-plane energy End
Enb E? Ehb Enb van der Waals interaction E?
electronstatic terms Enb hydrogen bonding
other interactions
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Energy Terms

• Eb two body bonding energy

E? three body valence angle energy
K?, ?
E? four body interaction torsional energy
K?, ?
K?, ?
E? four body interaction out-of-plane energy
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Energy Terms

• Enb van der Waals interaction

E? electronstatic terms
Enb hydrogen bonding other interactions
D
H
A
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Issues

• Spectroscopic effect parameter estimation
• Model effect metric
• Electronic effect - electrostatics
• Environment charge distribution
• Entropy effect - stability

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Computation

• Fitting of spectroscopic data to molecular
  mechanics model.
• Energy minimization in a multiple minimum
  condition.

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CAD Contributions

• Non-manifold model to facilitate flexible model
  construction
• Model manipulation and editing guided by atomic
  interactions physical, electrical, magnetic and
  chemical.
• Metric measurement distance, angle
• Visualization to reflect reaction / interaction
  and animation.
• Model integration.

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Current Work

• AFM measurement of adhesion between SAM and
  polymer
• Integration of Finite Element Analysis (FEA) with
  Molecular Modeling (MM).

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CAE Contributions

• Molecular mechanics model
• Interaction of physical, electrical, and magnetic
  fields
• Interfacial problem
• Energy field estimation and minimization
• Integration with macro model

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Summary

• There are existing commercial software available
  which provides a benchmark platform
• It is important to integrate the CAD and CAE
  applications to make the software useful.

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Thank you!