Protein Folding

1
Blake Boling
Tamara Schneider
Protein Folding
and Computational Techniques
What is Protein Folding?
Proteins are a sequence of unbranched amino
acids, which make the protein unique. If folded
wrongly, they do not function properly and can
cause human and animal diseases.
Implications of Misfolding
Protein folding is the process in which and amino
acid sequence assumes a functional three
dimensional structure by folding and coiling.
There are four protein structures

• Two possible tertiary structures
• Protein in a-helix structure
• Protein in ß-sheet structure

Two conformations of PrP (Prion) Left normal
PrPC Right proposed model of abnormal PrPSc
Distributed Computing Query from a single
computer using resources from other computers and
providing the results.
Computational Techniques
Several computing techniques to simplify and
study the folding of proteins have been
developed. Here are the most important examples,
some utilize others.
Protein Structure Prediction
The goal is to predict three-dimensional
structure of proteins from an amino acid sequence.

• Comparative Protein Modeling
• Uses previously solved structures as starting
  points
• In nature there are about 2000 distinct protein
  folding motifs that can be used as templates
• Two approaches Homology Modeling and Protein
  Threading
• Homology Modeling
• Based on the assumption that two homologous
  protein will share very similar structures
• Given a solved amino acid structure from a
  homologous protein, it is mutated into the
  unsolved structure
• Protein Threading
• Scans the amino acid sequence of an unknown
  structure against a database of solved
  structures
• A scoring function is used to assess the
  compatibility
• De Novo Structure Prediction
• Tries to establish three-dimensional protein
  structure from scratch
• Requires vast computational resources
• Based on stochastic methods to search possible
  solutions
• Requires supercomputers or distributed computing

Computational Simulations of Model ProteinsThe
Lattice Model

• Lattice proteins are highly simplified models of
  proteins
• Amino Acid sequence behave like single
  functional units
• Molecule folds to its least energy consuming
  state

http//www.bio.davidson.edu/Courses/Molbio/MolStud
ents/spring2003/Kogoy/protein.html
Cartoon of a hypothetical crystalline lattice
Background image Staphylococcal protein A, Z
Domain (http//www-nmr.cabm.rutgers.edu/photogall
ery/structures/html/page16.html)
Background image Staphylococcal protein A, Z
Domain (http//www-nmr.cabm.rutgers.edu/photogall
ery/structures/html/page16.html)
Background image Staphylococcal protein A, Z
Domain (http//www-nmr.cabm.rutgers.edu/photogall
ery/structures/html/page16.html)
Background image Staphylococcal protein A, Z
Domain (http//www-nmr.cabm.rutgers.edu/photogall
ery/structures/html/page16.html)