Acknowledgements
H.A. acknowledges TUBITAK 2211 Doctoral Fellowship Pro-
gram. N.T. thanks to the TUBITAK Career Development Program
(Project no: 117E192). T.D. acknowledges TUBITAK BIDEB
2218 Program.References
- The UniProt Consortium (2017) UniProt: the
universal protein knowledgebase. Nucleic
Acids Res 45:D158–D169.https://doi.org/
10.1093/nar/gkw1152 - Keskin O, Tuncbag N, Gursoy A (2016) Pre-
dicting protein-protein interactions from the
molecular to the proteome level. Chem Rev
116:4884–4909. https://doi.org/10.1021/
acs.chemrev.5b00683 - Pazos F, Bang J-W (2006) Computational pre-
diction of functionally important regions in
proteins. Curr Bioinforma 1:15–23.https://
doi.org/10.2174/157489306775330633 - Capra JA, Singh M (2007) Predicting func-
tionally important residues from sequence con-
servation. Bioinformatics 23:1875–1882.
https://doi.org/10.1093/bioinformatics/
btm270 - Keskin O, Tsai C-J, Wolfson H, Nussinov R
(2004) A new, structurally nonredundant,
diverse data set of protein-protein interfaces
and its implications. Protein Sci
13:1043–1055.https://doi.org/10.1110/ps.
03484604 - Tuncbag N, Gursoy A, Guney E et al (2008)
Architectures and functional coverage of pro-
tein–protein interfaces. J Mol Biol
381:785–802. https://doi.org/10.1016/j.
jmb.2008.04.071 - Bray T, Chan P, Bougouffa S et al (2009) Site-
sIdentify: a protein functional site prediction
tool. BMC Bioinformatics 10:379. https://
doi.org/10.1186/1471-2105-10-379 - Kc DB, Livesay DR (2011) Topology improves
phylogenetic motif functional site predictions.
IEEE/ACM Trans Comput Biol Bioinform
8:226–233.https://doi.org/10.1109/TCBB.
2009.60 - Pazos F, Valencia A (2001) Similarity of phylo-
genetic trees as indicator of protein-protein
interaction. Protein Eng 14:609–614.
https://doi.org/10.1093/protein/14.9.609 - Lichtarge O, Bourne HR, Cohen FE (1996)
An evolutionary trace method defines binding
surfaces common to protein families. J Mol
Biol 257:342–358. https://doi.org/10.
1006/jmbi.1996.0167- Landau M, Mayrose I, Rosenberg Y et al
(2005) ConSurf 2005: the projection of evolu-
tionary conservation scores of residues on pro-
tein structures. Nucleic Acids Res 33:
W299–W302. https://doi.org/10.1093/
nar/gki370 - Ashkenazy H, Abadi S, Martz E et al (2016)
ConSurf 2016: an improved methodology to
estimate and visualize evolutionary conserva-
tion in macromolecules. Nucleic Acids Res
44:W344–W350. https://doi.org/10.1093/
nar/gkw408 - Sankararaman S, Sjo ̈lander K (2008)
INTREPID--INformation-theoretic TREe
traversal for protein functional site IDentifica-
tion. Bioinformatics 24:2445–2452.https://
doi.org/10.1093/bioinformatics/btn474 - Lua RC, Wilson SJ, Konecki DM et al (2016)
UET: a database of evolutionarily-predicted
functional determinants of protein sequences
that cluster as functional sites in protein struc-
tures. Nucleic Acids Res 44:D308–D312.
https://doi.org/10.1093/nar/gkv1279 - Ofran Y, Rost B (2007) ISIS: interaction sites
identified from sequence. Bioinformatics 23:
e13–e16. https://doi.org/10.1093/bioinfor
matics/btl303 - de Juan D, Pazos F, Valencia A (2013)
Emerging methods in protein co-evolution.
Nat Rev Genet 14:249–261.https://doi.org/
10.1038/nrg3414 - Hopf TA, Sch€arfe CPI, Rodrigues JPGLM et al
(2014) Sequence co-evolution gives 3D con-
tacts and structures of protein complexes. eLife
3:1–45. https://doi.org/10.7554/eLife.
03430 - Rodriguez-Rivas J, Marsili S, Juan D, Valencia
A (2016) Conservation of coevolving protein
interfaces bridges prokaryote-eukaryote
homologies in the twilight zone. Proc Natl
Acad Sci U S A 113:15018–15023.https://
doi.org/10.1073/pnas.1611861114 - Gueudre ́ T, Baldassi C, Zamparo M et al
(2016) Simultaneous identification of
68 Heval Atas et al.