COMPUTATIONAL BIOLOGY AND COMPUTATIONAL CHEMISTRY
Project Leader:
Sorin Istrail (*)
The Tortilla Project:
Mathematical and Computational Methods for Protein Folding
Supported in part by DOE MICS Program, Fred Howes, Program Director
Massively Parallel Computing Research Laboratory
Sandia National Laboratories
Research Collaborations
Major collaborators:
- Professor Ken Dill, Department of Pharmaceutical Chemistry, University of
California, San Francisco
- Professor Jonathan King, Department of Biology, Massachusetts Institute
of Technology
- Professor Michael Waterman, Department of Mathematics, University of Southern California
Other Collaborators:
Serafim Batzoglou (MIT), Debbie Goldman (UC Berkeley),
Giuseppe Lancia (U of Padoa, Italy), Antonio Piccolboni (UC Davis and U of Milan, Italy)
Sandia Collaborator:
Media Coverage of Our Research
RESEARCH PROBLEMS
- Ab Initio Lattice Protein Folding
- Monte Carlo Simulations of Protein Misfolding
- Structure Alignment/ Fold Classification
- Contact Map Structure and Algorithms
- Computational Intractability of Protein Folding
- Protein Threading and Design
- Statistical Mechanics
- Tortilla Software Package
- Computing Low Energy Lattice Conformations with Guaranteed Error Bounds
- Computational Intractability Theorems: NP-completeness of Models
- Branch-and-Bound Search Methods
- Native Conformation Estimation Through Self-Assembly Methods
- Sequence Design
- Protein Misfolding/Aggregation/Inclusion Bodies
- Lattice vs. Off-Lattice Conformations
- HP Benchmarks
Recent Research Summary
The algorithms, software and graphics capabilities are incorporated
in the TORTILLA Protein Folding Software Package.
Some Images Related to Recent Research
The Protein Misfolding/Aggregation Problem
Joint work with
Russell Schwartz (MIT, Department of Computer Science) and
Jonathan King (MIT, Department of Biology).
Misfolding Funnel
Click on the images for more detail.
Lattice Protein Folding Algorithms
Joint work with
Serafim Batzoglou (MIT, Department of Computer Science),
Bill Hart (Sandia) and
Brian Walenz (University of New Mexico and Sandia)
A PDB protein of size about 300,
folded on the Face-Center Cubic lattice
to near optimality
(better than 99%
of the optimal number of contacts),
in the lattice HP-model with explicit side-chains.
Red spheres represent
hydrophobic side-chains,
blue spheres represent hydrophilic side-chains, and green
spheres (drawn smaller
for better
visibility of structure)
represent the protein backbone.
Mathematics of materials self-assembly used for rigorous estimate of the
lattice native conformations.
Click on images to enlarge them.
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Four snapshots of the hydrophobic packing in a protein conformation having energy better than 86%
of optimal.
Computational Molecular Recognition
Combinatorial Chemistry Methods in Molecular Recongition and Drug Design
Collaborators:
Debbie Goldman (UC Berkeley),
Giuseppe Lancia (U of Padoa, Italy), Antonio Piccolboni (UC Davis and U of Milan, Italy)
Sandia Collaborators:
Jean-Loup Faulon, Diana Roe, Brian Walenz
- Algorithm Design for Inverse Problems for Topological (2D) Chemical Indices and 3D Chemical Indices
Related to Lead Compound Optimization in the Design of Combinatorial Peptides
and Combinatorial Libraries
Multiple Biochemical Sequence Alignment
- Multiple Sequence Alignment and Voting Paradoxes
- Eigenvalue Methods in Multiple Alignment
Self-Assembly of Materials
Collaborators:
Sandia Collaborators:
Al Hurd, Frank van Swol, Brain Walenz
Nanobrick Self-Assembly
- Potts Models for Nanobrick Self-Assembly
- Prediction Algorithms for 2D and 3D Tiling with Energetically Programmed Surfaces.
Statistical Mechanics and Computational Complexity:
Ising Models
- Exact Determination Across Crystal Lattices of the Computational Tractability Frontier for the Ground States of the
Ising Spin Glass Zero Field Model
- Solutions to the Generalized Ferromagnetic Conjectures: 2D vs. Planarity, Second-Neighbor Interactions, 3D Ising
Exact Methods in Polymer Design
Sandia Collaborator:
Jean-Loup Faulon
Design of polynomial time algorithms for Group Aditivity
inverse problems for polymer design.
Genomic Mapping
Collaborator:
Serafim Batzoglou (MIT)
Combinatorial Methods for the STS Mapping with Repeated Probes: The Hypergraph Superstring Problem
(*) For more information about this project including:
* postdoctoral positions, * graduate summer student positions, * visitors, * availability and purchase of the
Tortilla Software Package, contact:
Sorin Istrail, Ph.D.,
Project Leader, Computational Biology and Computational Chemistry,
Sandia National Laboratories,
Massively Parallel Computing Research Laboratory,
MS 1110,
Albuquerque, NM 87185,
(505) 845-7612,
http://www.cs.sandia.gov/~scistra
scistra@cs.sandia.gov
Last update by Sorin Istrail, August 22, 1997
