How can we predict protein structures

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How can we predict protein structures?
Chen Keasar BGU
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An analysis of incorrectly folded protein models.
Implications for structure predictions. Novotny
J, Bruccoleri R, Karplus M. (J Mol Biol. 1984 Aug
25177(4)787-818. )
hemerythrin
imunoglubulin
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3D-1D profile Bowie, J. U., Luethy, R.,
Eisenberg, D. (1991). "A method to
identify protein sequences that fold into a known
three dimensional structure." Science, 253,
164-170.
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3D-1D profile Bowie, J. U., Luethy, R.,
Eisenberg, D. (1991). "A method to
identify protein sequences that fold into a known
three dimensional structure." Science, 253,
164-170.
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3D-1D profile Bowie, J. U., Luethy, R.,
Eisenberg, D. (1991). "A method to
identify protein sequences that fold into a known
three dimensional structure." Science, 253,
164-170.

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3D-1D profile Bowie, J. U., Luethy, R.,
Eisenberg, D. (1991). "A method to
identify protein sequences that fold into a known
three dimensional structure." Science, 253,
164-170.

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Miyazawa S. and Jernigan RL. Estimation of
Effective Inter-residue Contact Energies
from Protein Crystal Structures Quasi-Chemical
Approximation Macromolecules, 18534-552,
1985. Manfred J. Sippl Boltzmann's principle,
knowledge-based mean fields and protein folding.
An approach to the computational determination of
protein structures. Journal of Computer-Aided
Molecular Design 7(4) 473-501 (1993)
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D. Fischer 3D-SHOTGUN a novel, cooperative,
fold-recognition meta-predictor. Proteins. 2003
May 1551(3)434-41.
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3D- Jury a simple approach to improve
protein structure predictions,K. Ginalski, A.
Elofsson, D. Fischer L. Rychlewski
Bioinformatics Vol. 19 no. 8 2003, pages 1015
1018
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?????????????? (3D-SHOTGUN)
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?????????????? (3D-SHOTGUN)
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?????????????? (3D-SHOTGUN)
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?????????????? (3D-SHOTGUN)
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?????????????? (3D-SHOTGUN)
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Model Quality Assessment Programs (MQAPs)
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??? (???? ???? ????????? ?? Structural Genomics)?
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• ??? ????? ??????? ????? ?????? ? ORFane
  proteins.
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????? ???? ??????? ????? ???? ab-initio

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The energy function/representation dilemma.
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• A dream function
• ? Has a clear minimum in the native structure.
• ? Has a clear path towards the minimum.
• ? Global optimization algorithm should find the
  native structure.

Chen Keasar BGU
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• An approximate function
• ? Easier to design and compute.
• ? Native structure not always the global
  minimum.
• ? Global optimization methods do not converge.
  Many alternative models (decoys) should be
  generated.

Chen Keasar BGU
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• An approximate function
• ? Easier to design and compute.
• ? Native structure not always the global
  minimum.
• ? Global optimization methods do not converge.
  Many alternative models (decoys) should be
  generated.
• ? No clear way of choosing among them.

Chen Keasar BGU
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????? ???? clustering
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????? ???? clustering
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????? ???? clustering
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AMBR ECEP CHARM OPLS ENCAD GROMOS
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Levitt, Keasar
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Scheraga 1998
Levitt 1976
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Levitt, Keasar
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Levitt, Keasar
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Scheraga 1998
Levitt 1976
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Levitt, Keasar
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