TY - JOUR
T1 - Correlated mutations
T2 - Advances and limitations. A study on fusion proteins and on the Cohesin-Dockerin families
AU - Halperin, Inbal
AU - Wolfson, Haim
AU - Nussinov, Ruth
PY - 2006/6/1
Y1 - 2006/6/1
N2 - Correlated mutations have been repeatedly exploited for intramolecular contact map prediction. Over the last decade these efforts yielded several methods for measuring correlated mutations. Nevertheless, the application of correlated mutations for the prediction of intermolecular interactions has not yet been explored. This gap is due to several obstacles, such as 3D complexes availability, paralog discrimination, and the availability of sequence pairs that are required for inter- but not intramolecular analyses. Here we selected for analysis fusion protein families that bypass some of these obstacles. We find that several correlated mutation measurements yield reasonable accuracy for intramolecular contact map prediction on the fusion dataset. However, the accuracy level drops sharply in intermolecular contacts prediction. This drop in accuracy does not occmr always. In the Cohesin-Dockerin family, reasonable accuracy is achieved in the prediction of both intra- and intermolecular contacts. The Cohesin-Dockerin family is well suited for correlated mutation analysis. Because, however, this family constitutes a special case (it has radical mutations, has domain repeats, within each species each Dockerin domain interacts with each Cohesin domain, see below), the successful prediction in this family does not point to a general potential in using correlated mutations for predicting intermolecular contacts. Overall, the results of our study indicate that current methodologies of correlated mutations analysis are not suitable for large-scale intermolecular contact prediction, and thus cannot assist in docking. With current measurements, sequence availability, sequence annotations, and underdeveloped sequence pairing methods, correlated mutations can yield reasonable accuracy only for a handful of families.
AB - Correlated mutations have been repeatedly exploited for intramolecular contact map prediction. Over the last decade these efforts yielded several methods for measuring correlated mutations. Nevertheless, the application of correlated mutations for the prediction of intermolecular interactions has not yet been explored. This gap is due to several obstacles, such as 3D complexes availability, paralog discrimination, and the availability of sequence pairs that are required for inter- but not intramolecular analyses. Here we selected for analysis fusion protein families that bypass some of these obstacles. We find that several correlated mutation measurements yield reasonable accuracy for intramolecular contact map prediction on the fusion dataset. However, the accuracy level drops sharply in intermolecular contacts prediction. This drop in accuracy does not occmr always. In the Cohesin-Dockerin family, reasonable accuracy is achieved in the prediction of both intra- and intermolecular contacts. The Cohesin-Dockerin family is well suited for correlated mutation analysis. Because, however, this family constitutes a special case (it has radical mutations, has domain repeats, within each species each Dockerin domain interacts with each Cohesin domain, see below), the successful prediction in this family does not point to a general potential in using correlated mutations for predicting intermolecular contacts. Overall, the results of our study indicate that current methodologies of correlated mutations analysis are not suitable for large-scale intermolecular contact prediction, and thus cannot assist in docking. With current measurements, sequence availability, sequence annotations, and underdeveloped sequence pairing methods, correlated mutations can yield reasonable accuracy only for a handful of families.
KW - Binding site
KW - Correlated mutations
KW - Fusion proteins
KW - Protein-protein interactions
KW - Residue covariation
UR - http://www.scopus.com/inward/record.url?scp=33646766064&partnerID=8YFLogxK
U2 - 10.1002/prot.20933
DO - 10.1002/prot.20933
M3 - מאמר
C2 - 16508975
AN - SCOPUS:33646766064
VL - 63
SP - 832
EP - 845
JO - Proteins: Structure, Function and Bioinformatics
JF - Proteins: Structure, Function and Bioinformatics
SN - 0887-3585
IS - 4
ER -