Related Experiment Video
Updated: Jul 4, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
CUSP: an algorithm to distinguish structurally conserved and unconserved regions in protein domain alignments and its
Sankaran Sandhya1, Barah Pankaj, Madabosse Kande Govind
1National Centre for Biological Sciences (TIFR), UAS-GKVK Campus, Bellary Road, Bangalore 560 065, India. sandhya@ncbs.res.in
Background:
Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner. Further, we have used the method to characterize the length, structural type and biochemical features of indels in related protein domains.
Results:
CUSP, examines protein domain structural alignments to distinguish regions of conserved structure common to related proteins from structurally unconserved regions that vary in length and type of structure. On a non-redundant dataset of 353 domain superfamily alignments from PASS2, we find that 'length- deviant' protein superfamilies show > 30% length variation from their average domain length. 60% of additional lengths that occur in indels are short-length structures (< 5 residues) while 6% of indels are > 15 residues in length. Structural types in indels also show class-specific trends.
Conclusion:
The extent of length variation varies across different superfamilies and indels show class-specific trends for preferred lengths and structural types. Such indels of different lengths even within a single protein domain superfamily could have structural and functional consequences that drive their selection, underlying their importance in similarity detection and computational modelling. The availability of systematic algorithms, like CUSP, should enable decision making in a domain superfamily-specific manner.
Related Concept Videos
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Conservation of Protein Domains
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Multi-species Conserved Sequences
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Evolutionary Relationships through Genome Comparisons

