TY  - JOUR
T1  - In Silico Engineering of Brain Derived Neurotrophic Factor (BDNF) to Improve its
Neurogenerative Bioactivity
AU - Parvizian, Hajar AU - Keyhanfar, Mehrnaz AU - Ghaedi, Kamran AU - Etemadifar, Masoud AU - Kazem Farzandi, Najmeh 
JO  - Research Journal of Agronomy
VL  - 13
IS  - 4
SP  - 29
EP  - 35
PY  - 2019
DA  - 2001/08/19
SN  - 1815-9354
DO  - rjagr.2019.29.35
UR  - https://makhillpublications.co/view-article.php?doi=rjagr.2019.29.35
KW  - Brain
KW  -derived neurotrophic factor
KW  -bioinformatics
KW  -trkB
KW  -treatment
AB  - Brain Derived Neurotrophic Factor (BDNF),
Neurotrophin-3(NT-3), Neurotrophin-4/5 (NT-4/5) and
Neurotrophin-6 (NT-6) are known as neurotrophins.
BDNF secreted to extracellular and binds to the soluble
tropomyosin-related kinase B (trkB). Interaction of BDNF
to trkB is linked to several intracellular signal
transduction pathways such as Ras-MAP kinase cascade.
These cascades regulate neuronal development, plasticity,
long-term potentiation and synapses. BDNF is known to
exist in solution as homodimeric proteins. Also, this
protein forms heterodimer structures with Neurotrophin 4
(NT4) and Neurotrophin-3 (NT-3). The biological activity
of BDNF heterodimers was reported to be less active in
neuronal survival assays than a BDNF homodimers
structures. In this research, new structures of BDNF that
have better interaction with each other to form homodimer
was modelled. Therefore, the amino acids that participate
in interaction with BDNF were identified by search in
neurochemical evidences. The amino acids are Tyr112,
Tyr114 and Lys97. This amino acids were mutated by
swiss pdb viewer software. The predicted model was
submitted to 3Drefine server for optimization of hydrogen
bonding network and energy minimization. To analyzing
the predicted models, RAMPAGE and Qmean server
were used. Finally, binding interaction between new
structures of BDNF was done by using Hex.8.0.0
software. The results showed that interaction between
these structures is better than the two native BDNF.
Recently, researchers found that BDNF played an
important therapeutic role in many human
neurodegenerative diseases and this protein has potential
for the treatment of the diseases.
ER  -