Computational Protein Topographics for Health Improvement

1
Computational Protein Topographics for Health
Improvement Jie Liang, Ph.D. Bioengineering Prim
e Grant Support National Science Foundation
Career Award, National Institutes of Health R01,
Office of Naval Research, and the
Whitaker Foundation.
Protein surface matching
Problem Statement and Motivation

• The structure of proteins provide rich
  information about how cells work. With the
  success of structural genomics, soon we will have
  all human proteins mapped to structures.
• However, we need to develop computational tools
  to extract information from these structures to
  understand how cell works and how new diseases
  can be treated.
• Therefore, the development of computational tools
  for surface matching and for function prediction
  will open the door for many new development for
  health improvement.

Evolution of function
Key Achievements and Future Goals
Technical Approach

• We have developed a web server CASTP (cast.engr.
  uic.edu) that identify and measures protein
  surfaces. It has been used by thousands of
  scientists world wide.
• We have built a protein surface library for
  gt10,000 proteins, and have developed models to
  characterize cross reactivities of enzymes.
• We also developed methods for designing phage
  library for discovery of peptide drugs.
• We have developed methods for predicting
  structures of beta-barrel membrane proteins.
• Future Understand how protein fold and
  assemble, and designing method for engineering
  better proteins and drugs.

• We use geometric models and fast algorithm to
  characterize surface properties of over thirty
  protein structures.
• We develop evolutionary models to understand how
  proteins overall evolve to acquire different
  functions using different combination of surface
  textures.
• Efficient search methods and statistical models
  allow us to identify very similar surfaces on
  totally different proteins
• Probablistc models and sampling techniques help
  us to understand how protein works to perform
  their functions.

2
Fluid Physics and Transport Phenomena in the
Human Brain Laboratory for Product and Process
Design, Director A. A. LINNINGER College of
Engineering, University of Illinois, Chicago, IL,
60607, U.S.A. Grant Support NSF, Susman and
Asher Foundation

• Problem Statement
• Prediction of large deformations of the brain
  parenchyma based on Fluid-Structure Interaction
  modeling.
• Coupling of the brain parenchyma, vascular and
  ventricular system in the human brain.
• Motivation
• The therapeutic approach for hydrocephalus
  treatment is very brutal (shunting) and many
  revisions are needed.
• Ultimate goal precise model of human brain
  dynamics to design treatments without in vivo
  test.

• Key Achievements
• 3D geometric reconstruction of patient-specific
  brain dimensions based on MRI data
• 3D patient-specific dynamic analysis of CSF flow
  in the human brain
• Future Goals
• Optimal Drug Delivery to the Human Brain.
• Feedback control systems to better treat
  Hydrocephalus.

• Data from Magnetic Resonance Imaging.
• Use of MRI reconstruction tools for generation of
  3D patient specific brain geometry.
• Introduction of the geometry to Finite Volumes or
  Finite Elements advanced solvers.
• Post processing of the obtained results.

3
Integrating Nanostructures with Biological
Structures Investigators M. Stroscio, ECE and
BioE M. Dutta, ECE Prime Grant Support ARO,
NSF, AFOSR, SRC, DARPA
Problem Statement and Motivation
Quantum Dot

• Coupling manmade nanostructures with biological
  structures to monitor and control biological
  processes.
• For underlying concepts see Biological
  Nanostructures and Applications of Nanostructures
  in Biology Electrical, Mechanical, Optical
  Properties, edited by Michael A. Stroscio and
  Mitra Dutta (Kluwer, New York, 2004).

Cellular Membrane
Integrin
Technical Approach
Key Achievements and Future Goals

• Synthesis of nanostructures
• Binding nanostructures to manmade structures
• Modeling electrical, optical and mechanical
• properties of nanostructures
• Experimental characterization of intergated
  manmade
• nanostructure-biological structures

• Numerous manmade nanostructures have been
  functionalized with biomolecules
• Nanostructure-biomolecule complexes have been
  used to study a variety of biological structures
  including cells
• Interactions between nanostructures with
  biomolecules and with biological environments
  have been modeled for a wide variety of systems
• Ultimate goal is controlling biological systems
  at the nanoscale

4
Multimode Sonic Ultrasonic Diagnostic
Imaging Investigators Thomas J. Royston
Francis Loth, Mechanical Industrial
Engineering Prime Grant Support NIH
Problem Statement and Motivation
Bimodal image.

• Ultrasonic (US) imaging provides detailed
  geometry
• Geometric changes may indicate disease or injury
• Sonic imaging provides unique functional
  information
• Sounds associated with disease are sonic, not US
• Merge US and Sonics to harness strengths of each
• Initial application peripheral vascular
  pathologies vessel constrictions (plaque and
  intimal hyperplasia)

Blood vessel with constriction in soft tissue
phantom Grayscale of geometry from US
imaging Color overlay of acoustic field generated
by turbulence downstream of the constriction
Key Achievements and Future Goals
Technical Approach

• Sonic wave propagation in biological tissue is
  more complex than US.
• Requires new acoustic modeling developments
• Inverse modeling to extract acoustic image from
  array
• Novel acoustic sensor development

• Prototype US/Sonic system has been developed
• - conventional US system retrofitted with
• - electromagnetic position device for true
  3D imaging
• - acoustic sensor array pad that is
  transparent to US so US imaging can be conducted
  with the pad in place
• Calibration of system on phantom models in
  progress
• Turbulence imaged downstream of vessel
  constriction
• Future plans Human subject studies, improved
  prototype, better sensor array, improved imaging
  software

Prototype 15 sensor sonic array pad on arm

• Merging multiple imaging modalities on same
  platform

Biomedical Biotechnology