Protein Engineering, Vol. 14, No. 4, 219-226,
April 2001
© 2001 Oxford University Press
Use of a database of structural alignments and phylogenetic trees in investigating the relationship between sequence and structural variability among homologous proteins
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India
The database PALI (Phylogeny and ALIgnment of homologous protein structures) consists of families of protein domains of known three-dimensional (3D) structure. In a PALI family, every member has been structurally aligned with every other member (pairwise) and also simultaneous superposition (multiple) of all the members has been performed. The database also contains 3D structure-based and structure-dependent sequence similarity-based phylogenetic dendrograms for all the families. The PALI release used in the present analysis comprises 225 families derived largely from the HOMSTRAD and SCOP databases. The quality of the multiple rigid-body structural alignments in PALI was compared with that obtained from COMPARER, which encodes a procedure based on properties and relationships. The alignments from the two procedures agreed very well and variations are seen only in the low sequence similarity cases often in the loop regions. A validation of Direct Pairwise Alignment (DPA) between two proteins is provided by comparing it with Pairwise alignment extracted from Multiple Alignment of all the members in the family (PMA). In general, DPA and PMA are found to vary rarely. The ready availability of pairwise alignments allows the analysis of variations in structural distances as a function of sequence similarities and number of topologically equivalent C
atoms. The structural distance metric used in the analysis combines root mean square deviation (r.m.s.d.) and number of equivalences, and is shown to vary similarly to r.m.s.d. The correlation between sequence similarity and structural similarity is poor in pairs with low sequence similarities. A comparison of sequence and 3D structure-based phylogenies for all the families suggests that only a few families have a radical difference in the two kinds of dendrograms. The difference could occur when the sequence similarity among the homologues is low or when the structures are subjected to evolutionary pressure for the retention of function. The PALI database is expected to be useful in furthering our understanding of the relationship between sequences and structures of homologous proteins and their evolution.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Xu, J. Zhang, L. Wang, J. Zhou, H. Huang, J. Wu, Y. Zhong, and Y. Shi Solution structure of Urm1 and its implications for the origin of protein modifiers PNAS, August 1, 2006; 103(31): 11625 - 11630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lupyan, A. Leo-Macias, and A. R. Ortiz A new progressive-iterative algorithm for multiple structure alignment Bioinformatics, August 1, 2005; 21(15): 3255 - 3263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shapiro and D. Brutlag FoldMiner and LOCK 2: protein structure comparison and motif discovery on the web Nucleic Acids Res., July 1, 2004; 32(suppl_2): W536 - W541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. S. Gowri, S. B. Pandit, P. S. Karthik, N. Srinivasan, and S. Balaji Integration of related sequences with protein three-dimensional structural families in an updated version of PALI database Nucleic Acids Res., January 1, 2003; 31(1): 486 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Pandit, D. Gosar, S. Abhiman, S. Sujatha, S. S. Dixit, N. S. Mhatre, R. Sowdhamini, and N. Srinivasan SUPFAM--a database of potential protein superfamily relationships derived by comparing sequence-based and structure-based families: implications for structural genomics and function annotation in genomes Nucleic Acids Res., January 1, 2002; 30(1): 289 - 293. [Abstract] [Full Text] [PDF]
|
|