AUTODOCK

1. 20apch020

2. 1.INTRODUCTION
• Cyclodextrins are a family of cyclic oligosaccharides, consisting of
a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic
bonds. Cyclodextrins are produced
from starch by enzymatic conversion. They are used in food,
pharmaceutical, drug delivery, and chemical industries, as well as
agriculture and environmental engineering.[1]
• Cyclodextrins are composed of 5 or more α-D-glucopyranoside
units linked 1->4, as in amylose (a fragment of starch). The largest
cyclodextrin contains 32 1,4-anhydroglucopyranoside units, while as
a poorly characterized mixture, at least 150-membered cyclic
oligosaccharides are also known. Typical cyclodextrins contain a
number of glucose monomers ranging from six to eight units in a
ring, creating a cone shape:

3. Clasiffication of cyclodextrin
• α (alpha)- Cyclodextrin: 6 glucose subunits
• β (beta)-cyclodextrin : 7 glucose subunits
• γ (gamma)-cyclodextrin: 8 glucose subunits
α (alpha)- Cyclodextrin:
sometimes abbreviated as α-CD, is a hexasaccharide derived from glucose.
It is related to the β- (beta) and γ- (gamma) cyclodextrins, which contain seven
and eight glucose units, respectively. All cyclodextrins are white, water-soluble
solids with minimal toxicity. Cyclodextrins tend to bind other molecules in
their quasi-cylindrical interiors. This inclusion (and release) behavior leads to
applications in medicine.[1] The compound is of wide interest because it
exhibits host–guest properties, forming inclusion compounds.
β (beta)-cyclodextrin
β-Cyclodextrin (β-CD) is a cone-shaped molecule. It is hydrophilic at the
outer surface of the cavity for many hydroxyl groups, but hydrophobic in the
cavity. So β-CD is soluble in water, and a variety of hydrophobic guest
molecules can be encapsulated in its non-polar cavity.

4. γ (gamma)-cyclodextrin
Gamma-cyclodextrin (gamma-CD) is a cyclic alpha-(1,4)-linked
oligosaccharide consisting of eight glucose molecules. Like other
cyclodextrins, gamma-CD can form inclusion complexes with a variety of
organic molecules because the inner side of the torus-like molecule is less
polar than the outer side.
Structural of Cyclodextrins
The three cyclodextrins, alpha CD (α-CD), beta CD (β-CD), and
gamma CD (γ-CD), have six, seven, and eight D-glucose subunits,
respectively, and their structures are shown in Figure 2. The D-glucose
subunit typically assumes a 4C1 chair conformation (Figure 3), and
sometimes, though less frequently, the 1C4 chair conformation[48-52]. The
chair conformation of the D-glucose subunit overall CD angular strain. It
also puts the “bulky” oxygen groups (hydroxyls, glycosidic groups) into the
equatorial plane[53], further stabilizing the CD.

5. Figure:α-CD (1),β-CD(2),γ-CD(3)
Figure:4

6. • Figure 4. The three native CDs, α-CD, β-CD, and γ-CD, form a truncated cone
(right) instead of the symmetrical cone (left). n = 6, 7, and 8, for α-CD, β-CD,
and γ-CD, respectively
Figure:5
Figure 5. Primary and secondary hydroxyls point towards the outside of the
cyclodextrin molecule

7. Mebendazole is methyl 5-benzoylbenzimidazole-2-carbamate and has the following
structural formula:
Molecular Formula: C16H13N3O3
Mebendazole is usually well tolerated. Common side effects include headache,
vomiting, and ringing in the ears. If used at large doses it may cause bone marrow
suppression. It is unclear if it is safe in pregnancy. Mebendazole is a broad-
spectrum antihelminthic agent of the benzimidazole type
Mebendazole

8. • Mebendazole acts as an anti-tubulin agent, demonstrating
inhibition of tubulin polymerization in several cancer cell lines,
and has, therefore, also been proposed as a substitute for vincristine
in the treatment of brain tumors
Mebendazole, a well-known anti-helminthic drug in wide
clinical use, has anti-cancer properties that have been elucidated in
a broad range of pre-clinical studies across a number of different
cancer types.
Uses
• You may take this medicine with or without food.
• Chew it completely before swallowing. Do not swallow the tablet
whole.
• If you have trouble chewing the tablet, place it in a spoon and add 2
to 3 mL of drinking water by using a dosing syringe.
• The tablet will absorb the water within 2 minutes and turns into a
soft mass with semi-solid consistency, which you can swallow it.

9. Dosing
• For oral dosage form (Emverm™ chewable tablets):
• For common roundworms, hookworms, and whipworms:
– Adults and children 2 years of age and older—100 milligrams
(mg) two times a day, morning and evening, for 3 consecutive
days. Treatment may need to be repeated in 3 weeks.
– Children younger than 2 years of age—Use and dose must be
determined by your doctor.

10. 2. Method
Types of Docking
Program Year Published License
AADS 2011 Free to usewebservice
ADAM 1994 Commercial
AutoDock 1990 Open source (GNU GPL)
AutoDock Vina 2010 Open source (Apache License)
AutoDock Version 4.2
Automated docking of ligand to macromolecule by Lamarckian Genetic
Algorithm and Empirical Free Energy Scoring Function.
AutoDock is a molecular modeling simulation software. It is especially
effective for protein-ligand docking. AutoDock 4 is available under
the GNU General Public License. AutoDock is one of the most
cited docking software applications in the research community

11. • " This guide includes information on the methods and files used by
AutoDock and information on use of AutoDockTools to generate
these files and to analyze results.
Instalation softwere
• AutoDock and AutoDockTools, the graphical user interface
for AutoDock are available on the WWW at:
• http://autodock.scripps.edu/
• The WWW site also includes many resources for use of AutoDock,
including detailed Tutorials that guide users through basic AutoDock
usage, docking with flexible rings, and virtual screening with
AutoDock.
copy two files from the below path
C:Program Files (x86)The Scripps Research
InstituteAutodock4.2.6 from the distination folder copy
autodock4 & autogrid4past those two files in your working
directory/folder.

12. * next Molecule and lidand prepare to ``mol 2” file.
Figure
OPEN BABLE ICON
Open Babel: https://openbabel.org/wiki/Category:I...
copy two files from the below path
C:Program Files (x86)open Bable 1.5.6Libsite-
packagesAutoDockToolsfrom the distination folder
copy AD4.1_bound.dat & AD4_parameters.dat past
those two files in your working directory/folder

13. 4 STEPS
STEP 1: Preparing Coordinates
STEP 2: Running AutoGrid
STEP 3: Docking with AutoDock
STEP 4: Evaluating the Results of a Docking

14. Rank Sub-Rank Run Binding Energy Cluster
RMSD
Reference
RMSD
Grep
Patteren
1 1 2 -8.33 0.00 111.74 RANKING
1 2 9 -8.31 0.10 111.73 RANKING
1 3 6 -7.93 1.64 111.48 RANKING
1 4 10 -7.90 0.94 111.62 RANKING
1 5 1 -7.88 0.96 111.70 RANKING
1 6 4 -7.86 0.94 111.60 RANKING
1 7 7 -7.85 0.94 111.64 RANKING
1 8 3 -7.76 1.30 111.57 RANKING
1 9 8 -7.67 1.81 111.81 RANKING
2 1 5 -7.35 0.00 111.96 RANKING
The higher Binding Energy value in the table[-8.33]
Result And Discussion
α -CD

15. Docking with α-Cyclodextrin inclusion with
Mebandazole Drug

16. β -CD
Rank Sub Rank Run Binding Energy Cluster
RMSD
Reference
RMSD
Grep
Pattern
1 1 8 -6.14 0.00 39.23 RANKING
1 2 1 -6.08 1.67 40.09 RANKING
2 1 2 -6.00 0.00 40.66 RANKING
2 2 5 -5.97 0.23 40.68 RANKING
2 3 3 -5.94 0.52 40.83 RANKING
3 1 4 -5.96 0.00 40.12 RANKING
3 2 9 -5.94 0.07 40.14 RANKING
4 1 6 -5.95 0.00 39.42 RANKING
5 1 10 -5.91 0.00 38.14 RANKING
6 1 7 -5.83 0.00 38.61 RANKING
The higher Binding Energy value in the table[-6.14]

17. Docking with β-Cyclodextrin inclusion
with Mebandazole Drug

18. Rank Sub -rank Run Binding Energy Cluster
RMSD
Reference
RMSD
Grep
Pattern
1 1 5 -6.41 0.00 107.54 RANKING
1 2 2 -6.39 0.22 107.50 RANKING
1 3 10 -6.31 0.63 107.59 RANKING
1 4 1 -6.27 0.90 107.73 RANKING
2 1 3 -6.38 0.00 109.00 RANKING
2 2 9 -6.25 1.03 108.66 RANKING
3 1 6 -6.22 0.00 110.51 RANKING
3 2 8 -5.52 1.69 110.45 RANKING
4 1 7 -6.00 0.00 107.58 RANKING
4 2 4 -5.73 1.87 106.85 RANKING
γ –CD The higher Binding Energy value in the table[-
6.41]

19. Docking with γ-Cyclodextrin inclusion with
Mebandazole Drug

20. • Binding Energy Value:
-6.14< -6.41 < -8.33
β-CD< γ-CD < α-CD

21. THE END