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PMID: 17976239 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Determinants of protein function revealed by combinatorial entropy optimization.

Genome biology ·Vol. 8 ·No. 11 ·2007-00-00 ·Pages R232

Reva B, Antipin Y, Sander C

Abstract

We use a new algorithm (combinatorial entropy optimization [CEO]) to identify specificity residues and functional subfamilies in sets of proteins related by evolution. Specificity residues are conserved within a subfamily but differ between subfamilies, and they typically encode functional diversity. We obtain good agreement between predicted specificity residues and experimentally known functional residues in protein interfaces. Such predicted functional determinants are useful for interpreting the functional consequences of mutations in natural evolution and disease.

MeSH Terms
Algorithms Amino Acid Sequence Cell Cycle Proteins/chemistry,genetics,physiology Combinatorial Chemistry Techniques Entropy Evolution, Molecular GTP Phosphohydrolases/chemistry,genetics,physiology Humans Molecular Sequence Data Sequence Homology, Amino Acid
Chemicals
Cell Cycle Proteins GTP Phosphohydrolases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Reva Boris
Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. borisr@mskcc.org
Antipin Yevgeniy
Sander Chris
References (33)
33 references, click to expand
  1. A family of evolution-entropy hybrid methods for ranking protein residues by importance.
    J Mol Biol. 2004 Mar 5;336(5):1265-82 PMID: 15037084
  2. Detection of conserved physico-chemical characteristics of proteins by analyzing clusters of positions with co-ordinated substitutions.
    Bioinformatics. 2001 Nov;17(11):1035-46 PMID: 11724732
  3. Automated selection of positions determining functional specificity of proteins by comparative analysis of orthologous groups in protein families.
    Protein Sci. 2004 Feb;13(2):443-56 PMID: 14739328
  4. A sequence property approach to searching protein databases.
    J Mol Biol. 1995 Aug 18;251(3):390-9 PMID: 7650738
  5. Universally conserved positions in protein folds: reading evolutionary signals about stability, folding kinetics and function.
    J Mol Biol. 1999 Aug 6;291(1):177-96 PMID: 10438614
  6. An evolutionary trace method defines binding surfaces common to protein families.
    J Mol Biol. 1996 Mar 29;257(2):342-58 PMID: 8609628
  7. Evolutionarily conserved networks of residues mediate allosteric communication in proteins.
    Nat Struct Biol. 2003 Jan;10(1):59-69 PMID: 12483203
  8. MView: a web-compatible database search or multiple alignment viewer.
    Bioinformatics. 1998;14(4):380-1 PMID: 9632837
  9. Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function.
    Genomics. 2004 Jun;83(6):970-9 PMID: 15177551
  10. Structure-based mutagenesis reveals distinct functions for Ras switch 1 and switch 2 in Sos-catalyzed guanine nucleotide exchange.
    J Biol Chem. 2001 Jul 20;276(29):27629-37 PMID: 11333268
  11. Co-evolutionary analysis reveals insights into protein-protein interactions.
    J Mol Biol. 2002 Nov 15;324(1):177-92 PMID: 12421567
  12. SCOP: a structural classification of proteins database for the investigation of sequences and structures.
    J Mol Biol. 1995 Apr 7;247(4):536-40 PMID: 7723011
  13. Distinct structural elements of rab5 define its functional specificity.
    EMBO J. 1994 Feb 1;13(3):575-83 PMID: 8313902
  14. The Pfam protein families database.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41 PMID: 14681378
  15. Likelihood models of somatic mutation and codon substitution in cancer genes.
    Genetics. 2003 Oct;165(2):695-705 PMID: 14573481
  16. The HSSP database of protein structure-sequence alignments.
    Nucleic Acids Res. 1996 Jan 1;24(1):201-5 PMID: 8594579
  17. Correlated mutations contain information about protein-protein interaction.
    J Mol Biol. 1997 Aug 29;271(4):511-23 PMID: 9281423
  18. Tumor suppressor genes: at the crossroads of molecular carcinogenesis, molecular epidemiology and human risk assessment.
    Lung Cancer. 2001 Dec;34 Suppl 2:S7-15 PMID: 11720736
  19. Molecular basis for Rho GTPase signaling specificity.
    Breast Cancer Res Treat. 2004 Mar;84(1):61-71 PMID: 14999155
  20. Bayesian search of functionally divergent protein subgroups and their function specific residues.
    Bioinformatics. 2006 Oct 15;22(20):2466-74 PMID: 16870932
  21. Residues of the Rho family GTPases Rho and Cdc42 that specify sensitivity to Dbl-like guanine nucleotide exchange factors.
    J Biol Chem. 1997 Feb 21;272(8):4671-9 PMID: 9030518
  22. Rho GTPases: biochemistry and biology.
    Annu Rev Cell Dev Biol. 2005;21:247-69 PMID: 16212495
  23. A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls.
    Cancer. 2004 Apr 1;100(7):1345-51 PMID: 15042666
  24. Evolutionarily conserved pathways of energetic connectivity in protein families.
    Science. 1999 Oct 8;286(5438):295-9 PMID: 10514373
  25. Predicting specificity-determining residues in two large eukaryotic transcription factor families.
    Nucleic Acids Res. 2005 Aug 05;33(14):4455-65 PMID: 16085755
  26. A method to predict functional residues in proteins.
    Nat Struct Biol. 1995 Feb;2(2):171-8 PMID: 7749921
  27. Switch-of-function mutants based on morphology classification of Ras superfamily small GTPases.
    Cell. 2003 May 2;113(3):315-28 PMID: 12732140
  28. Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure.
    J Mol Biol. 2001 Nov 2;313(4):903-19 PMID: 11697912
  29. Correlated mutation analyses on very large sequence families.
    Chembiochem. 2002 Oct 4;3(10):1010-7 PMID: 12362367
  30. Detailed computational study of p53 and p16: using evolutionary sequence analysis and disease-associated mutations to predict the functional consequences of allelic variants.
    Oncogene. 2003 Feb 27;22(8):1150-63 PMID: 12606942
  31. Specificity determinants on Cdc42 for binding its effector protein ACK.
    Biochemistry. 2005 Sep 20;44(37):12373-83 PMID: 16156650
  32. Optimization of protein structure on lattices using a self-consistent field approach.
    J Comput Biol. 1998 Fall;5(3):531-8 PMID: 9773348
  33. The protein kinase resource.
    Trends Biochem Sci. 1997 Nov;22(11):444-6 PMID: 9397688
Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/gb-2007-8-11-r232
Email
borisr@mskcc.org
Published
2007-00-00
Pages
R232
Language
English
Region
England
NLM ID
100960660
PMCID
PMC2258190
Subset
IM
External Links
PubMed source DOI: 10.1186/gb-2007-8-11-r232 PMC Full Text View journal details
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