Objective:
The present study delineates
the
generation of mutant peptide library from a known anticancer peptide, p21
and
in silico
evaluation
for
their
affinity towards cyclin
. A substrate binding groove.
Method
s:
Mutant
peptide library
was created based on their AntiCP
score
and was docked with cyclin A using ClusPro2.0 web server. The docked
structures were further simulated into an aqueous environment using Gromacs 4.5.6. Visualization was
performed using PyMol software and
interaction analysis was done using Discovery Studio Visualizer 4.1 Client and LigPlot plus tool.
Result
s:
A total of 57 mutant peptides were generate
d;
out of which only 3 namely, K3C
(Lys3Cys)
, K3F
(Lys3Phe)
, and K3W (
Lys3Trp)
had
a
greater
affinity for cyclin A than
WILD
p21 peptide
(HSKRRLIFS
). Molecular dynamic s
imulation studies showed that
the
peptides remained docked
into the substrate binding groove throughout the run. Among all the peptides, K3C
showed
a
significantly higher
negative binding energy
with
cyclin A
as
compar
ed
to WILD.
Conclusio
n:
The
overall
results
suggested that
K3C
mutant peptide had ~30 % higher affinity towards cyclin A and thus, could further be explored
for its anticancer potential. The study also
provides
an insight into the crucial interactions governing the recognition of substrate binding groove of
cyclin A for
the
development
of novel peptide
-based
anticancer therapeutics