Atomistic modeling of the structural components of the

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Transcript Atomistic modeling of the structural components of the 

Atomistic modeling of the
structural components of the bloodbrain barrier
Olga Glukhova, Sararov State University,
Russia
Olga Grishina, Sararov State University,
Russia
Michail Slepchenkov, Sararov State
University, Russia
Actuality
Blood-brain barrier, which is a barrage system
between the brain and blood vessels, plays a key role
in the "isolation" of the brain of unnecessary
information, and reduce the "noise" in the
interneuron communication. It is known that the
barrier function of the BBB strictly depends on the
initial state of the organism and changes significantly
with age and, especially in developing the "vascular
accidents. Disclosure mechanisms of regulation of the
barrier function will develop new ways to deliver
neurotrophic drugs to the brain in the newborn.
The aim of this work is the
construction of atomistic models
of structural components of the
blood-brain barrier to reveal the
mechanisms of regulation of the
barrier function.
Atomistic Modeling
π‘˜π‘ (𝑏 βˆ’ 𝑏0 )2
𝑉 𝑅 =
Amber Force Field
π‘π‘œπ‘›π‘‘π‘ 
π‘˜πœƒ (πœƒ βˆ’ πœƒ0 )2 +
+
π‘Žπ‘›π‘”π‘’π‘™π‘ 
π‘˜πœ‘ cos π‘›πœ‘ + 𝛿 + 1 +
π‘‘π‘œπ‘Ÿπ‘ π‘–π‘œπ‘›π‘ 
[
π‘›π‘œπ‘›π‘π‘œπ‘›π‘‘
π‘π‘Žπ‘–π‘Ÿπ‘ 
π‘žπ‘– π‘žπ‘— 𝐴𝐴𝑖𝑗 𝐢𝑖𝑗
+ 12 βˆ’ 6 ]
π‘Ÿπ‘–π‘—
π‘Ÿπ‘–π‘—
π‘Ÿπ‘–π‘—
The first three summations
are
over
bonds
(1-2
interactions), angles
(1-3 interactions), and
torsions (1-4 interactions).
FORCE FIELDS FOR
PROTEIN SIMULATIONS
By JAY W. PONDER AND
DAVID A. CASE
HARLEM Molecular Modeling Package
was used for atomistic modeling
MARTINI COARSE-GRAINED
Uk ο€½ Vbond  Vangle  Vdihedral  Vnonbond
Vbond

1
ο€½ οƒ₯ K ki rki ο€­ rki0
i 2

2
Vangle ο€½ οƒ₯ M jki (cos( jki ) ο€­ cos( 0jki ))2
iο‚Ή j
1
Vdihedral ο€½ οƒ₯ Π€ljki (1  cos( ljki ο€­  ljki ))
i 2
  οƒΆ12   οƒΆ6 οƒΉ
qi qk
ik
ik
οƒ·οƒ· ο€­ 
οƒ·οƒ· οƒΊ  οƒ₯
Vnonbond ο€½ οƒ₯ 4ο₯ ik οƒͺ
i ο‚Ήk
οƒͺ rik οƒΈ
 rik οƒΈ  i ο‚Ή k 4ο₯ο₯ 0rik
All-atomistic modeling of BBR
components
Biologically active domain of cadherin is a sequence
of 213 amino acids. The structure of this protein was
obtained in 2002 and his polnoatomnaya model
stored in the Protein Data Bank (4-Boggon, TJ,
Murray, J., Chappuis-Flament, S., Wong, E.,
Gumbiner, BM, Shapiro, L. C- cadherin ectodomain
structure and implications for cell adhesion
mechanisms. Journal: (2002) Science 296: 13081313). The primary structure of the antibody specific
for the cadherin consisting of 784 amino acid
sequenced in 2013.
All-atomic structure of Cadherin
Coarse-grained structure of Cadherin
All-atomic structure of Cadherin
All-atomic structure of anticadgerin
Coarse-grained structure of Anticadherin