The Protein Threading Problem With Sequence Amino Acid Interaction Preferences Is NPComplete - PowerPoint PPT Presentation

1 / 14
About This Presentation
Title:

The Protein Threading Problem With Sequence Amino Acid Interaction Preferences Is NPComplete

Description:

Predict protein structure using amino acid interaction preferences. Result ... Interactions between amino acids from the sequence are admitted into the score function ... – PowerPoint PPT presentation

Number of Views:48
Avg rating:3.0/5.0
Slides: 15
Provided by: chengba
Category:

less

Transcript and Presenter's Notes

Title: The Protein Threading Problem With Sequence Amino Acid Interaction Preferences Is NPComplete


1
The Protein Threading Problem With Sequence Amino
Acid Interaction Preferences Is NP-Complete
  • Richard H. Lathrop
  • Artificial Intelligence Laboratory, MIT
  • Presenter Chengbang Huang
  • Oct. 26 2004

2
Introduction
  • Protein consists of amino acids
  • Amino acid interaction decides protein structure
  • Predict protein structure using amino acid
    interaction preferences

3
Result
  • The Protein Threading Decision Problem----does
    there exist a threading with a score less than K,
    is NP-complete, under two following assumptions
  • Variable-length gaps are admitted into the
    alignment
  • Interactions between amino acids from the
    sequence are admitted into the score function

4
Difficulties of Direct Prediction
  • Direct approach---find the folded conformation
    with minimum energy
  • Delicate energetic balance of powerful atomic
    forces
  • Vast number of possible conformations
  • Forces involved poorly understood or difficult to
    model accurately
  • Summation over a large number of atoms

5
Alternative
  • Use the known protein structures as spatial
    folding templates
  • Only around 1,000 different protein structural
    families (Chothia, 1992)
  • Each known protein structure recognizes protein
    sequences likely to fold into a similar structure.

6
Implementation
  • The known structure provides a set of positions
    in 3-dimensional space, represented by an
    adjacency graph.
  • These will be filled by amino acids from a
    sequence of known structure
  • Different candidate threadings arise
  • A score function can distinguish good from bad
    threadings

7
2 Assumptions
  • Variable-length gaps are admitted into the
    alignment
  • Interactions between amino acids from the
    sequence are admitted into the score function

8
Approaches w/o 2 Assumptions
  • Fixed-length moving window, Crippen 1990
  • Pro focus closely on the score function, which
    can be devised to identify correct match
  • Con ignore variable-length gap, structure and
    sequence could be out of registration
  • Ignore interactions between neighboring amino
    acids, Bowie et al. 1991
  • Pro Simpler, sometimes perform well
  • Con Give up structure information
  • Both are accomplished in polynomial time.

9
To Prove NP-Completeness
  • Problem is in NP
  • Transform a known NP-complete problem to the
    problem studied. Encoding and decoding take
    polynomial time.

10
Transform to 1-in-3 3SAT problem
  • SATisfiability a set of Boolean variables, plus
    a set of Boolean clauses. Does there exist any
    setting of variables that makes all the clauses
    true simultaneously?
  • 3SAT clauses contain exactly 3 literals
  • 1-in-3 3SAT each of the clauses can be made true
    by exactly one of the three literals.

11
Sketch of Proof
  • Threading with a score of zero encode solutions
    of the original 1-in-3 3SAT problem
  • Threadings with positive scores encode failures.

12
More Details
  • True---Threonine, False---Phenalanine
  • P (proline) first literal Q (glutamine)
    second R (arginine) third
  • The sequence a to be threaded is
  • aPQRPQRPQRPQRTFTFTF
  • one PQR for each clause, one TF for each
    Boolean Variable.

13
Discussion
  • Any protein threading algorithm must adopt one of
    the following choices
  • Fail to admit variable-length gaps
  • Fail to admit interaction preferences
  • Fail to find the optimal threading
  • Require an exponential amount of time

14
(No Transcript)
Write a Comment
User Comments (0)
About PowerShow.com