| dc.description.abstract | The valine to glutamate substitution at the 600th residue of B-type rapidly
accelerated fibrosarcoma protein (BRAF V600E) is the most common mutation in
the BRAF gene. Due to its high prevalence in a number of cancers, the development
of efficient diagnostic and prognostic assays and therapeutics is essential for their
management. Aptamers have become promising candidates in a variety of
biomedical applications due to many favourable properties. However, no aptamers
that can distinguish the V600E mutation status of the BRAF protein have been
experimentally determined. Therefore, this study was conducted to create an initial
knowledge base for in silico design of aptamers for wild-type and mutant (V600E)
BRAF (mutant BRAF) proteins. It was achieved using molecular docking employing
HADDOCK 2.4 web server. In the absence of aptamers for BRAF, five RNA aptamers
targeted to the activation loop of ERK 1&2 proteins were selected for docking,
considering the similarity of the 3D structure of the kinase domains of the above
proteins to BRAF. Docking was done for ten protein-aptamer combinations (five
aptamers with wild-type BRAF and mutant BRAF). Three complexes were selected
based on the HADDOCK score and their intermolecular hydrogen bonds and salt
bridges were determined. Three aptamers obtained negative HADDOCK scores
signifying that they presumably target the activation loop of wild-type and mutant
BRAF. Considering the total intermolecular hydrogen bonds and salt bridges,
Aptamers_1 and 3 (Apta-Index IDs: 481 and 263) would preferably bind with wildtype
and mutant BRAF, respectively. They have the potential to be used as starting
structures in the in-silico aptamer modeling workflow for wild-type and mutant
BRAF proteins. | en_US |
