49
software; however specific steps should be altered. The tutorial is
designed for working in a Linux machine.
1. You may download the desired molecules (CC and 2-HP-B- CD)
from chemical databases such as http://www.chemspider.com/
or alternatively use a chemical modeling software such as
Schrodinger’s Maestro 3D builder [9] in order to create the 3D
structures of the drug molecule CC and the host molecule
2-HP-B-CD. If you decide to use chemspider.com search for
“candesartan
cilexetil”
and
“2-hydroxypropyl-beta-cyclodextrin.”
2. Open UCSF Chimera [10] or any chemical modeling software
in order to manually put the drug molecule inside the CD’s
cavity.
3. In Chimera click File → Open, choose the CC molecule that
you downloaded from a database or created with a modeling
software and save it on your workstation.
4. Do the same for 2-HP-B-CD.
5. Now, both molecules should be visible in the Chimera window.
Select CC by Ctrl+Left Click on one atom of the CC molecule.
Press the up arrow (↑) in order to expand the selection to the
whole molecule.
6. Click Tools → Movement → Movement Mouse Mode. In the
Movement Mouse Mode dialog box choose “Move Selection”
and minimize the dialog box.
7. Now move the molecule by pressing the middle mouse button
until you put it in the CD’s cavity.
8. Go again in the Movement Mouse Mode that you previously
minimized and choose “Normal.” Now the whole system can
be rotated by clicking the left mouse button. Always check
every perspective by rotating around in order to visualize that
the molecule is indeed inside the cavity. Do not mind if any
clashes are present since the structure will be minimized later.
9. In order to deselect click Select → Clear Selection.
The crude complex structure needs to be energetically minimized
by performing a geometry optimization.
1. In the Chimera environment, click Tools → Structure
Editing → Minimize Structure. Keep the default settings and
click minimize and OK in all dialog boxes that appear. After a
while (depending on your machine’s capacity) the minimization will be complete and a “Finished” indication will appear in
the bottom- left Chimera window. Save the final complex structure in .pdb format by pressing File → Save pdb and save it as
3.1 System
Preparation
3.1.1 Manually Create
the Drug: CD Complex
3.1.2 Minimize Structure
Study of Candesartan Cilexetil: 2-Hydroxypropyl-β-Cyclodextrin Interactions…
software; however specific steps should be altered. The tutorial is
designed for working in a Linux machine.
1. You may download the desired molecules (CC and 2-HP-B- CD)
from chemical databases such as http://www.chemspider.com/
or alternatively use a chemical modeling software such as
Schrodinger’s Maestro 3D builder [9] in order to create the 3D
structures of the drug molecule CC and the host molecule
2-HP-B-CD. If you decide to use chemspider.com search for
“candesartan
cilexetil”
and
“2-hydroxypropyl-beta-cyclodextrin.”
2. Open UCSF Chimera [10] or any chemical modeling software
in order to manually put the drug molecule inside the CD’s
cavity.
3. In Chimera click File → Open, choose the CC molecule that
you downloaded from a database or created with a modeling
software and save it on your workstation.
4. Do the same for 2-HP-B-CD.
5. Now, both molecules should be visible in the Chimera window.
Select CC by Ctrl+Left Click on one atom of the CC molecule.
Press the up arrow (↑) in order to expand the selection to the
whole molecule.
6. Click Tools → Movement → Movement Mouse Mode. In the
Movement Mouse Mode dialog box choose “Move Selection”
and minimize the dialog box.
7. Now move the molecule by pressing the middle mouse button
until you put it in the CD’s cavity.
8. Go again in the Movement Mouse Mode that you previously
minimized and choose “Normal.” Now the whole system can
be rotated by clicking the left mouse button. Always check
every perspective by rotating around in order to visualize that
the molecule is indeed inside the cavity. Do not mind if any
clashes are present since the structure will be minimized later.
9. In order to deselect click Select → Clear Selection.
The crude complex structure needs to be energetically minimized
by performing a geometry optimization.
1. In the Chimera environment, click Tools → Structure
Editing → Minimize Structure. Keep the default settings and
click minimize and OK in all dialog boxes that appear. After a
while (depending on your machine’s capacity) the minimization will be complete and a “Finished” indication will appear in
the bottom- left Chimera window. Save the final complex structure in .pdb format by pressing File → Save pdb and save it as
3.1 System
Preparation
3.1.1 Manually Create
the Drug: CD Complex
3.1.2 Minimize Structure
Study of Candesartan Cilexetil: 2-Hydroxypropyl-β-Cyclodextrin Interactions…