Thermoelectric Properties of Fe0.2Co3.8Sb12-xTex ... - Physics

Using cis peptide containing fragments for functional annotation
of proteins
Sreetama Das 1 , Suryanarayanarao Ramakumar 1 and Debnath Pal 2
1 Department of Physics, 2 Supercomputer Education Research Centre, Indian Institute of
Science, Bangalore 560012, India
BACKGROUND: Proteins are linear polymers of the twenty naturally occurring amino
acids, and are essential for many cellular processes. The consecutive amino acids are
covalently linked by a peptide bond, which may be in cis or trans conformation. There are a
large number of proteins whose structures are known but their functions are not. Here from
arises the need for protein function prediction methods.
Cis peptide bonds, and especially those involving non-Proline amino acids, although rare in
occurrence in protein structures, are implicated to play an important role in their structure
and/ or function. It is, therefore, pertinent to ask if singular protein segments containing cis
peptides can provide functional annotation of proteins with known structure but unknown
function.
RESULTS:
We used our own protein backbone geometry-based clustering algorithm to group cis peptide
containing fragments of specific lengths. Of these we identified fragments of length 6 ─ 8,
suitable for annotation studies. Grouped fragments of these lengths were subjected to analysis
of enrichment of Gene Ontology (GO) molecular function terms. Fragments associated with
statistically-enriched GO terms were identified as functionally important. These functionally
“significant” fragments were thereafter searched in homologous proteins. Their utility as
singular cis-containing peptide fragment for providing functional annotation was thereafter
confirmed through a high area under the Receiver-Operator-Curve (ROC). Subsequently, we
are attempting to locate these fragments in proteins of unknown function for annotation
purposes.
CONCLUSIONS:
Fragments associated with enriched GO molecular function showing propensities ≥ 20 and p-
value thresholds ≤ 0.05 point to cis peptide-containing fragments important for protein
function. This fact was verified through a literature survey. When used for identifying similar
fragments in a set of non-redundant entries from the PDB database, the fragments alone were
sufficient to identify close homologues and related proteins. Currently, we are establishing
the utility of these fragments for functionally annotating proteins with no known function.