1. The document describes a computational framework for interacting with physical molecular models of polypeptide chains. It involves developing physical models of proteins using 3D printing and interfacing them with computational tools.
2. The framework aims to enable new scientific discovery through a tactile, geometric approach that is complementary to existing computational modeling of proteins.
3. The physical models are parameterized so they can be customized based on protein data and interfaced with computer simulations, allowing comparison to online databases.
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Promita Chakraborty Dissertation (Copyright 2014) -- A Computational Framework for Interacting with Physical Molecular Models of the Polypeptide Chain
1. 1
A Computational Framework
for Interacting with Physical
Molecular Models of the
Polypeptide Chain
Promita Chakraborty
Mar 26, 2014
PhD Dissertation Final Defense
Blacksburg, Virginia Tech
Peppytides
2. 2
A computational paradigm
1 2 3
• N: data from native protein structures, experimental analysis and observations
• C: existing computational models
• P: form-specific physical models of proteins
4. 4
Folding of polypeptides
Polypeptide, before and after folding
Source: http://en.wikipedia.org/wiki/Protein_folding
pid: 2R73,Trichosurin, milk whey protein
6. 6
A new way of looking at
the old problem
• Tactile, geometrical, spatial approach
• Complementary to computational
approach
• Enable new scientific discovery
Khatib, Baker et al. Crystal structure of a monomeric retroviral protease solved by protein
folding game players, Nature Structural &. Mol. Biol., 18 (2011)
9. 9
Existing models
CPK models
Dreiding stereomodel
Ball-and-stick
Center for
BioMolecular
Modeling, Milwaukee
School of Engineering
http://www.
3dmoleculardesigns.com/
Scripps Physical Model
Service, Scripps Research
Institute
http://models.scripps.edu/
beta sheet
alpha helix
DNA double helix
Gillet, Olson et al. Tangible Interfaces for Structural Molecular Biology,
Structure, 13 (2005)
13. 13
Atom-radii = 0.6 RVDW
Atom-radii = 0.7 RVDW
Atom-radii = 0.8 RVDW
"
Measured at 5˚ intervals
Ramachandran plot generated using
~80,000 structures from Protein Data
bank
16. 16
Energy plot (OPLS force field)
Peppytides at 0.7 RVDW with rotational barrier constraints
Ramachandran plots:A comparison
PDB data
Chakraborty and Zuckermann. Coarse-grained, foldable,
physical model of the polypeptide chain. PNAS,110 (33), (2013)
17. 17
Hydrogen bond
• Representing with magnets
• acceptor/donor as N/S pole
O–N distance is typically
3.00 ± 0.12 Å, from an α-
helix crystal structure
In the Peppytide model, the
O–N distance is 1.17 ̋ ±
0.04 ̋ (equivalent to 3.18 ±
0.11 Å)
29. 29
Interfacing with computer
• User-friendly printing of
customized and
parameterized physical
models
• Molecular simulation for the
physical model
• Comparison with online
databases
Collaboration with AutoDesk Inc.
31. 31
Peptide structure represented
by series of dihedral angles
• It is possible to describe the backbone structure by a sequence of phi psi angles?*
Residue #
Phi
Psi
1
-65
-40
2
-65
-40
...
-65
-40
Peptide bond angle
table representation
Backbone trace of
the same
polypeptide chain
A polypeptide
chain s native
conformation
*Ranganathan, Izotov, Kraka, and Cremer. Classification of Supersecondary Structures in Proteins Using the Automated Protein Structure Analysis Method. Arxiv preprint. (2008)
31
35. 35
Augmented Reality
DuploTrack: Object
tracking with lego blocks using
Microsoft Kinect camera
Gupta et al. DuploTrack: A Realtime System for
Authoring and Guiding Duplo Block Assembly.,
UIST, (2012)
Autodesk 123D Catch
Scan-Modify-Print philosophy
To:
Structure determination -
Human-scale abstraction -
3D-print -
Fold
36. 36
Two Self folding techniques
With permission from:
Skylar Tibbits
Dept. of Architecture,
MIT
37. 37
Outreach/user study
At Lawrence Hall of Science
museum, UC Berkeley
In collaboration with Maia Werner-Avidon and Lisa Newton
at Lawrence Hall of Science museum, UC Berkeley
38. 38
How to make them?
Open source
STL files available at www.peppytide.org
Make Magazine -- Projects
http://makezine.com/projects/peppytides/
40. 40
Acknowledgments
• Prof. Alexey Onufriev, Virginia Tech (Chair Co-advisor)
• Dr. Ronald Zuckermann (Co-advisor)
• Prof. Joseph DeRisi, UCSF (Committee member)
• Prof. Naren Ramakrishnan (Committee member)
• Prof. Liqing Zhang (Committee member)
• Molecular Foundry, Lawrence Berkeley National Laboratory
• Lawrence Hall of Science Museum, UC Berkeley
• Molecular Graphics and Computation Facility at UC Berkeley
• Industry Collaboration and support by Autodesk Inc.
This work was performed at the Molecular Foundry, Lawrence Berkeley National Laboratory, and was supported by the Defense
Threat Reduction Agency and the Office of Science, Office of Basic Energy Sciences, Scientific User Facilities Division, of the
U.S. Department of Energy under Contract No. DE-AC02—05CH11231.