Covalent Library Preparation 2024

2024-05-21T19:46:51Z

Mtsukanov:

2023-09-21T19:53:17Z

Mtsukanov:

== Step 1. Coding the Reactions ==
*Pick out the reactions that you want to enumerate. This can be done either through already-made reactions that are in commons.docking.org or you can use those reaction SMARTS and inclusion/exclusion SMARTS as examples/guidelines to make your own reaction/s. We recommend using the daylight SMARTS as a resource if you plan on doing this: https://www.daylight.com/dayhtml/doc/theory/theory.smarts.html.
*Once you have your reaction we recommend testing the inclusion and exclusion SMARTS through our website which has many modules and tools called TLDR. We have a specific tool called BBfilter(https://tldr.docking.org/start/bbfilter) that outputs building blocks from a large database based on the inclusion and exclusion SMARTS that are provided. Based on the correctness of the molecules that are outputted, the in/exclusion SMARTS should be adjusted to fit your needs.
*Once all the SMARTS have been finalized you can either submit this reaction into our reaction database called ChemistryCommons at commons.docking.org and email us once you do or email the SMARTS directly to us("chemistry4biology at gmail dot com") so that we can set your reaction up on the cluster.
== Step 2. Setting Up ==
*After you have made your reaction you are ready to get them ready on the cluster. If you don't have an account on the cluster already please email us at "chemistry4biology at gmail dot com" to help you get set up. Login into your cluster account and make sure you are in your home directory.
*Next, you will need to make a directory in your home directory that will store the enumeration results: "'''mkdir <name>'''".
*Then you will need to copy the necessary scripts over and this can be done by doing: "'''cp /nfs/exj/Fe/scripts .'''" .
*You will also need to copy an example reaction directory by doing: "'''cp /nfs/exj/Fe/Test .'''" . Use "'''mv Test <name>'''" to change the name into whatever you'd like.
*"'''cd <changed name>'''" into this directory to then change the parameters. To keep things simple you can just type "'''vim Reaction'''" press '''i''' and then change the id's to the ones of your reaction and in/exclusion rules. Then press '''esc''' and type ''':wq!''' to save.
*Next, ssh into a node such as n-1-18("'''ssh n-1-18'''") so that you're able to meet the requirements to run the scripts and then source the environment by doing "'''source /nfs/home/ak87/exa/UCSF/SynthI/BESPOKE/arthor-env/bin/activate'''" to get all the necessary packages for the scripts run.
== Step 3. Running the Scripts and Building Your Library ==
Congratulations you have completed the setup and are ready to run enumeration. All you need to do now is go into your reaction directory by using the command '''cd <name>''' and the run the script with "'''bash ../scripts/Etest.bash .'''". After enumeration is completed cd into your results directly and your enumerated file should be located inside!

[[Category: enumeration]]
[[Category: Chemistry Commons]]

CLI Enumeration

2023-09-21T19:52:12Z

Mtsukanov:

2023-08-10T18:52:37Z

Mtsukanov:

CLI Enumeration

2023-08-10T18:51:56Z

Mtsukanov: Created page with "== Coding the Reactions == Step 1. Pick out the reactions that you want to enumerate. This can be done either through already-made reactions that are in commons.docking.org or you can use those reaction SMARTS and inclusion/exclusion SMARTS as examples/guidelines to make your own reaction/s. We recommend using the daylight SMARTS as a resource if you plan on doing this: https://www.daylight.com/dayhtml/doc/theory/theory.smarts.html. Once you have your reaction we recomme..."

== Coding the Reactions ==
Step 1. Pick out the reactions that you want to enumerate. This can be done either through already-made reactions that are in commons.docking.org or you can use those reaction SMARTS and inclusion/exclusion SMARTS as examples/guidelines to make your own reaction/s. We recommend using the daylight SMARTS as a resource if you plan on doing this: https://www.daylight.com/dayhtml/doc/theory/theory.smarts.html. Once you have your reaction we recommend testing the inclusion and exclusion SMARTS through our website which has many modules and tools called TLDR. We have a specific tool called BBfilter(https://tldr.docking.org/start/bbfilter) that outputs building blocks from a large database based on the inclusion and exclusion SMARTS that are provided. Based on the correctness of the molecules that are outputted, the in/exclusion SMARTS should be adjusted to fit your needs. Once all the SMARTS have been finalized you can either submit this reaction into our reaction database called ChemistryCommons at commons.docking.org and email us once you do or email the SMARTS directly to us(mtsukanov at berkeley dot edu) so that we can set your reaction up on the cluster.
== Setting UP ==
Step 2. After you have made your reaction you are ready to run it on the cluster. If you don't have an account on the cluster already please email our lab member Khanh Tang at khtang015 at gmail dot com to help you get set up. Login into your cluster account and make sure you are in your home directory. Next, you will need to make a directory in your home directory that will store the enumeration results: "'''mkdir <name>'''". Then you will need to copy the necessary scripts over and this can be done by doing: "'''cp /nfs/exj/Fe/scripts .'''" . You will also need to copy an example reaction directory by doing: "'''cp /nfs/exj/Fe/Test .'''" . Use "'''mv Test <name>'''" to change the name into whatever you'd like. Next ssh into a node such as n-1-18 so that you're able to meet the requirements to run the scripts.

Particle Shape Calculator for CCDC/Mercury

2023-05-23T21:25:02Z

Mtsukanov: /* VisualHabit */

This tutorial will introduce you to the morphology calculation features included
with Mercury under the CSD-Particle toolset, namely BFDH Morphology and
VisualHabit.
BFDH crystal morphology is an approximation based on crystallographic
geometrical considerations. For a given structure, the BFDH algorithm will predict
the habit or shape of a crystal using the corresponding unit cell and symmetry
operator information.
The VisualHabit tool calculates a morphology for your material based on its
crystal structure. Using a range of forcefields, we can calculate the intermolecular
interactions, or synthons, in a crystal structure; the sum of these gives the lattice
energy for that system. From these lattice energies, we can calculate slice energies
and, consequently, the attachment energy for each slice. Crystal growth rates
assumed to be proportional to these attachment energies and can be used to
predict crystal shapes. The VisualHabit tool is used to calculate and analyze these
energies and to visualize the resulting morphologies, an instrumental step in
enabling solid form and particle design for small molecule crystal structures

==BFDH==
1. Open Mercury by double-clicking the Mercury icon on the desktop.

2. In the Structure Navigator toolbar type the refcode KAXXAI10.

3. We want to identify facets of interest in this morphology. We will first create
the morphology using the BFDH morphology feature.

4. From the top-level menu select CSD-Particle > Morphology > BFDH… to
generate the morphology. BFDH morphology uses the unit cell to create the
morphology you see, therefore it does not account for the chemistry of the
structure.

5. Rotate the structure to view the various facets that have been generated. If
you wish, explore options in the Morphology window.

6. The morphology can be modified, for example, if you want to represent a
crystal observed from growth experiments. In the Morphology window, click
Save… and place the .cif file in a folder where you have permission.

7. Using a text editor of your choice open the morphology .cif file. You will see
the data that corresponds to the HKLs and perpendicular distances. You can
modify these values to change the morphology. For the sake of example, we will
simply switch the values of some of the perpendicular distances. Note that
these changes are not based on experimental observation

8. Back in Mercury, In the Morphology window click Open… and select your
modified .cif file to visualize your new morphology

==VisualHabit==

The shape of a crystal results from the relative growth rates in different
directions. Strong intermolecular interactions, or synthons, in one direction, can
result in elongated crystal shapes like needles forming. Needle-shaped crystals
are common in pharmaceuticals and are undesirable due to their poor processing
characteristics. Being able to predict needle formation from a crystal structure is
helpful to understand potential manufacturing challenges.

1. Launch Mercury by clicking its icon. In the Structure Navigator toolbar,
type UREAXX to bring up the structure for urea.

2. Click on the CSD-Particle menu, select Morphology, then select VisualHabit…

3. In the VisualHabit dialogue box, you will see several options. On the left, you
will find options to change the calculation settings, such as which forcefield
is used and the limiting radius for the calculation. You can also choose
whether to add an electrostatic correction or not. On the right you will see
where the lattice energy results will appear once the calculation is complete.
For the purposes of this tutorial, we will keep the default options. These
typically work well for most situations, but if you know you are looking at
specific chemistry or a charged system, you may want to change these
settings.

4. Click the Calculate button to start.

5. The dialogue box will now update to show the results of the VisualHabit
calculation. The lattice energy results are shown in the section on the right in
kJ mol-1. From here, you can see the total lattice energy as well as the
contributions from the electrostatic, van der Waals, and hydrogen bonding
energy terms. It’s clear from these results that the lattice energy for urea is
dominated by the hydrogen bonding energy in the crystal structure.

6. The convergence chart shows how the lattice energy changes over the course
of the calculation out to the limiting radius and gives an indication of whether
the calculation has converged successfully (indicated by the green tick at the
bottom of the chart). This chart tells us that the lattice energy comes close to
its final value in a small distance for this structure. Urea is a small molecule,
so this is what we would expect to see.

7. If we look at the Mercury visualizer, we will see that the calculated
morphology for urea is now shown. VisualHabit calculates an elongated
morphology for urea where the long axis is aligned to the polar axis of the
urea molecule.

8. We will now explore the reasons for this elongated shape by examining the
nature of the intermolecular interactions, or synthons, in more detail. Click
on the Synthons tab in the VisualHabit dialogue to change the information
that is shown.

9. The synthons that contribute to the lattice energy, along with the centroid-centroid
distance and component energy terms, are now shown. Click on the
Interaction Energy header (you may need to scroll along to see it) to sort this
column from the strongest interaction to the weakest. Once again, you will
see that the lattice energy for urea is dominated by a small number of strong
hydrogen bonding interactions.

10. Now let’s look at the two most important interactions. Click on one of the
rows in the table to highlight that interaction and show the synthon in the
Mercury visualizer. You can select multiple rows by holding down Ctrl and
clicking on the rows of interest. Holding down Shift and clicking will let you select
multiple rows at once. Select the top two interactions for UREAXX
(synthons 8 and 9).

11. You will see in the Mercury visualizer that two other urea molecules have
appeared above and below the central molecule. The red dashed lines
between the molecules highlight the synthon, and the value beside the line
shows the interaction energy. You can clearly see that the strongest
interaction in urea aligns with the fastest growth direction.

12. Click the Visualiser tab in the VisualHabit dialogue. From this tab you can
change the way that the morphology is displayed in Mercury, such as
changing the colour of the faces and the edges. You can also change how
synthons are displayed.

13. Click the radio dial in the Synthons section to display Distance rather than
Energy.

14. The Mercury visualizer will update to show the centroid-centroid distance of
the synthons in Å. These short, strong types of hydrogen bonds in the crystal
structure of urea are key to understanding its growth and the shape of its
crystals.

==Conclusion==
Crystal shape is governed by the relative growth rates in different directions.
Strong intermolecular interactions, or synthons, in one direction can result in
elongated morphologies. The crystal structure of urea is dominated by strong
hydrogen bonding interactions that occur in tapes that propagate along the
crystallographic c-axis. This results in an elongated morphology for urea.

You should now know how to calculate a morphology using VisualHabit for a
CSD structure in Mercury and how to visualize and explore the key interactions
in that structure relative to the calculated crystal shape.

Particle Shape Calculator for CCDC/Mercury

2023-05-23T21:22:56Z

Mtsukanov: /* BFDH */

This tutorial will introduce you to the morphology calculation features included
with Mercury under the CSD-Particle toolset, namely BFDH Morphology and
VisualHabit.
BFDH crystal morphology is an approximation based on crystallographic
geometrical considerations. For a given structure, the BFDH algorithm will predict
the habit or shape of a crystal using the corresponding unit cell and symmetry
operator information.
The VisualHabit tool calculates a morphology for your material based on its
crystal structure. Using a range of forcefields, we can calculate the intermolecular
interactions, or synthons, in a crystal structure; the sum of these gives the lattice
energy for that system. From these lattice energies, we can calculate slice energies
and, consequently, the attachment energy for each slice. Crystal growth rates
assumed to be proportional to these attachment energies and can be used to
predict crystal shapes. The VisualHabit tool is used to calculate and analyze these
energies and to visualize the resulting morphologies, an instrumental step in
enabling solid form and particle design for small molecule crystal structures

==BFDH==
1. Open Mercury by double-clicking the Mercury icon on the desktop.

2. In the Structure Navigator toolbar type the refcode KAXXAI10.

3. We want to identify facets of interest in this morphology. We will first create
the morphology using the BFDH morphology feature.

4. From the top-level menu select CSD-Particle > Morphology > BFDH… to
generate the morphology. BFDH morphology uses the unit cell to create the
morphology you see, therefore it does not account for the chemistry of the
structure.

5. Rotate the structure to view the various facets that have been generated. If
you wish, explore options in the Morphology window.

6. The morphology can be modified, for example, if you want to represent a
crystal observed from growth experiments. In the Morphology window, click
Save… and place the .cif file in a folder where you have permission.

7. Using a text editor of your choice open the morphology .cif file. You will see
the data that corresponds to the HKLs and perpendicular distances. You can
modify these values to change the morphology. For the sake of example, we will
simply switch the values of some of the perpendicular distances. Note that
these changes are not based on experimental observation

8. Back in Mercury, In the Morphology window click Open… and select your
modified .cif file to visualize your new morphology

==VisualHabit==

The shape of a crystal results from the relative growth rates in different
directions. Strong intermolecular interactions, or synthons, in one direction, can
result in elongated crystal shapes like needles forming. Needle-shaped crystals
are common in pharmaceuticals and are undesirable due to their poor processing
characteristics. Being able to predict needle formation from a crystal structure is
helpful to understand potential manufacturing challenges.

1. Launch Mercury by clicking its icon. In the Structure Navigator toolbar,
type UREAXX to bring up the structure for urea.

2. Click on the CSD-Particle menu, select Morphology, then select VisualHabit…
3. In the VisualHabit dialogue box, you will see several options. On the left, you
will find options to change the calculation settings, such as which forcefield
is used and the limiting radius for the calculation. You can also choose
whether to add an electrostatic correction or not. On the right you will see
where the lattice energy results will appear once the calculation is complete.
For the purposes of this tutorial, we will keep the default options. These
typically work well for most situations, but if you know you are looking at
specific chemistry or a charged system, you may want to change these
settings.
4. Click the Calculate button to start.
5. The dialogue box will now update to show the results of the VisualHabit
calculation. The lattice energy results are shown in the section on the right in
kJ mol-1
. From here, you can see the total lattice energy as well as the
contributions from the electrostatic, van der Waals, and hydrogen bonding
energy terms. It’s clear from these results that the lattice energy for urea is
dominated by the hydrogen bonding energy in the crystal structure.
6. The convergence chart shows how the lattice energy changes over the course
of the calculation out to the limiting radius and gives an indication of whether
the calculation has converged successfully (indicated by the green tick at the
bottom of the chart). This chart tells us that the lattice energy comes close to
its final value in a small distance for this structure. Urea is a small molecule,
so this is what we would expect to see.
7. If we look at the Mercury visualizer, we will see that the calculated
morphology for urea is now shown. VisualHabit calculates an elongated
morphology for urea where the long axis is aligned to the polar axis of the
urea molecule.
8. We will now explore the reasons for this elongated shape by examining the
nature of the intermolecular interactions, or synthons, in more detail. Click
on the Synthons tab in the VisualHabit dialogue to change the information
that is shown.
9. The synthons that contribute to the lattice energy, along with the centroid-centroid
distance and component energy terms, are now shown. Click on the
Interaction Energy header (you may need to scroll along to see it) to sort this
column from the strongest interaction to the weakest. Once again, you will
see that the lattice energy for urea is dominated by a small number of strong
hydrogen bonding interactions.
10. Now let’s look at the two most important interactions. Click on one of the
rows in the table to highlight that interaction and show the synthon in the
Mercury visualizer. You can select multiple rows by holding down Ctrl and
clicking on the rows of interest. Holding down Shift and clicking will let you select
multiple rows at once. Select the top two interactions for UREAXX
(synthons 8 and 9).
11. You will see in the Mercury visualizer that two other urea molecules have
appeared above and below the central molecule. The red dashed lines
between the molecules highlight the synthon, and the value beside the line
shows the interaction energy. You can clearly see that the strongest
interaction in urea aligns with the fastest growth direction.
12. Click the Visualiser tab in the VisualHabit dialogue. From this tab you can
change the way that the morphology is displayed in Mercury, such as
changing the colour of the faces and the edges. You can also change how
synthons are displayed.
13. Click the radio dial in the Synthons section to display Distance rather than
Energy.
14. The Mercury visualizer will update to show the centroid-centroid distance of
the synthons in Å. These short, strong types of hydrogen bonds in the crystal
structure of urea are key to understanding its growth and the shape of its
crystals.

==Conclusion==
Crystal shape is governed by the relative growth rates in different directions.
Strong intermolecular interactions, or synthons, in one direction can result in
elongated morphologies. The crystal structure of urea is dominated by strong
hydrogen bonding interactions that occur in tapes that propagate along the
crystallographic c-axis. This results in an elongated morphology for urea.

You should now know how to calculate a morphology using VisualHabit for a
CSD structure in Mercury and how to visualize and explore the key interactions
in that structure relative to the calculated crystal shape.

Particle Shape Calculator for CCDC/Mercury

2023-05-23T21:21:34Z

Mtsukanov: /* BFDH */

This tutorial will introduce you to the morphology calculation features included
with Mercury under the CSD-Particle toolset, namely BFDH Morphology and
VisualHabit.
BFDH crystal morphology is an approximation based on crystallographic
geometrical considerations. For a given structure, the BFDH algorithm will predict
the habit or shape of a crystal using the corresponding unit cell and symmetry
operator information.
The VisualHabit tool calculates a morphology for your material based on its
crystal structure. Using a range of forcefields, we can calculate the intermolecular
interactions, or synthons, in a crystal structure; the sum of these gives the lattice
energy for that system. From these lattice energies, we can calculate slice energies
and, consequently, the attachment energy for each slice. Crystal growth rates
assumed to be proportional to these attachment energies and can be used to
predict crystal shapes. The VisualHabit tool is used to calculate and analyze these
energies and to visualize the resulting morphologies, an instrumental step in
enabling solid form and particle design for small molecule crystal structures

==BFDH==
1. Open Mercury by double-clicking the Mercury icon on the desktop.

2. In the Structure Navigator toolbar type the refcode KAXXAI10.

3. We want to identify facets of interest in this morphology. We will first create
the morphology using the BFDH morphology feature.

4. From the top-level menu select CSD-Particle > Morphology > BFDH… to
generate the morphology. BFDH morphology uses the unit cell to create the
morphology you see, therefore it does not account for the chemistry of the
structure.

5. Rotate the structure to view the various facets that have been generated. If
you wish, explore options in the Morphology window.

6. In the following exercises you may decide to calculate the BFDH morphology
to compare the results.

7. The morphology can be modified, for example, if you want to represent a
crystal observed from growth experiments. In the Morphology window, click
Save… and place the .cif file in a folder where you have permission.

8. Using a text editor of your choice open the morphology .cif file. You will see
the data that corresponds to the HKLs and perpendicular distances. You can
modify these values to change the morphology. For the sake of example, we will
simply switch the values of some of the perpendicular distances. Note that
these changes are not based on experimental observation

9. Back in Mercury, In the Morphology window click Open… and select your
modified .cif file to visualize your new morphology

==VisualHabit==

The shape of a crystal results from the relative growth rates in different
directions. Strong intermolecular interactions, or synthons, in one direction, can
result in elongated crystal shapes like needles forming. Needle-shaped crystals
are common in pharmaceuticals and are undesirable due to their poor processing
characteristics. Being able to predict needle formation from a crystal structure is
helpful to understand potential manufacturing challenges.

1. Launch Mercury by clicking its icon. In the Structure Navigator toolbar,
type UREAXX to bring up the structure for urea.

2. Click on the CSD-Particle menu, select Morphology, then select VisualHabit…
3. In the VisualHabit dialogue box, you will see several options. On the left, you
will find options to change the calculation settings, such as which forcefield
is used and the limiting radius for the calculation. You can also choose
whether to add an electrostatic correction or not. On the right you will see
where the lattice energy results will appear once the calculation is complete.
For the purposes of this tutorial, we will keep the default options. These
typically work well for most situations, but if you know you are looking at
specific chemistry or a charged system, you may want to change these
settings.
4. Click the Calculate button to start.
5. The dialogue box will now update to show the results of the VisualHabit
calculation. The lattice energy results are shown in the section on the right in
kJ mol-1
. From here, you can see the total lattice energy as well as the
contributions from the electrostatic, van der Waals, and hydrogen bonding
energy terms. It’s clear from these results that the lattice energy for urea is
dominated by the hydrogen bonding energy in the crystal structure.
6. The convergence chart shows how the lattice energy changes over the course
of the calculation out to the limiting radius and gives an indication of whether
the calculation has converged successfully (indicated by the green tick at the
bottom of the chart). This chart tells us that the lattice energy comes close to
its final value in a small distance for this structure. Urea is a small molecule,
so this is what we would expect to see.
7. If we look at the Mercury visualizer, we will see that the calculated
morphology for urea is now shown. VisualHabit calculates an elongated
morphology for urea where the long axis is aligned to the polar axis of the
urea molecule.
8. We will now explore the reasons for this elongated shape by examining the
nature of the intermolecular interactions, or synthons, in more detail. Click
on the Synthons tab in the VisualHabit dialogue to change the information
that is shown.
9. The synthons that contribute to the lattice energy, along with the centroid-centroid
distance and component energy terms, are now shown. Click on the
Interaction Energy header (you may need to scroll along to see it) to sort this
column from the strongest interaction to the weakest. Once again, you will
see that the lattice energy for urea is dominated by a small number of strong
hydrogen bonding interactions.
10. Now let’s look at the two most important interactions. Click on one of the
rows in the table to highlight that interaction and show the synthon in the
Mercury visualizer. You can select multiple rows by holding down Ctrl and
clicking on the rows of interest. Holding down Shift and clicking will let you select
multiple rows at once. Select the top two interactions for UREAXX
(synthons 8 and 9).
11. You will see in the Mercury visualizer that two other urea molecules have
appeared above and below the central molecule. The red dashed lines
between the molecules highlight the synthon, and the value beside the line
shows the interaction energy. You can clearly see that the strongest
interaction in urea aligns with the fastest growth direction.
12. Click the Visualiser tab in the VisualHabit dialogue. From this tab you can
change the way that the morphology is displayed in Mercury, such as
changing the colour of the faces and the edges. You can also change how
synthons are displayed.
13. Click the radio dial in the Synthons section to display Distance rather than
Energy.
14. The Mercury visualizer will update to show the centroid-centroid distance of
the synthons in Å. These short, strong types of hydrogen bonds in the crystal
structure of urea are key to understanding its growth and the shape of its
crystals.

==Conclusion==
Crystal shape is governed by the relative growth rates in different directions.
Strong intermolecular interactions, or synthons, in one direction can result in
elongated morphologies. The crystal structure of urea is dominated by strong
hydrogen bonding interactions that occur in tapes that propagate along the
crystallographic c-axis. This results in an elongated morphology for urea.

You should now know how to calculate a morphology using VisualHabit for a
CSD structure in Mercury and how to visualize and explore the key interactions
in that structure relative to the calculated crystal shape.

Particle Shape Calculator for CCDC/Mercury

2023-05-23T21:20:46Z

Mtsukanov: /* VisualHabit */

This tutorial will introduce you to the morphology calculation features included
with Mercury under the CSD-Particle toolset, namely BFDH Morphology and
VisualHabit.
BFDH crystal morphology is an approximation based on crystallographic
geometrical considerations. For a given structure, the BFDH algorithm will predict
the habit or shape of a crystal using the corresponding unit cell and symmetry
operator information.
The VisualHabit tool calculates a morphology for your material based on its
crystal structure. Using a range of forcefields, we can calculate the intermolecular
interactions, or synthons, in a crystal structure; the sum of these gives the lattice
energy for that system. From these lattice energies, we can calculate slice energies
and, consequently, the attachment energy for each slice. Crystal growth rates
assumed to be proportional to these attachment energies and can be used to
predict crystal shapes. The VisualHabit tool is used to calculate and analyze these
energies and to visualize the resulting morphologies, an instrumental step in
enabling solid form and particle design for small molecule crystal structures

==BFDH==
1. Open Mercury by double-clicking the Mercury icon on the desktop.
2. In the Structure Navigator toolbar type the refcode KAXXAI10.
3. We want to identify facets of interest in this morphology. We will first create
the morphology using the BFDH morphology feature.
4. From the top-level menu select CSD-Particle > Morphology > BFDH… to
generate the morphology. BFDH morphology uses the unit cell to create the
morphology you see, therefore it does not account for the chemistry of the
structure.
5. Rotate the structure to view the various facets that have been generated. If
you wish, explore options in the Morphology window.
6. In the following exercises you may decide to calculate the BFDH morphology
to compare the results.
7. The morphology can be modified, for example, if you want to represent a
crystal observed from growth experiments. In the Morphology window, click
Save… and place the .cif file in a folder where you have permission.
8. Using a text editor of your choice open the morphology .cif file. You will see
the data that corresponds to the HKLs and perpendicular distances. You can
modify these values to change the morphology. For the sake of example, we will
simply switch the values of some of the perpendicular distances. Note that
these changes are not based on experimental observation
9. Back in Mercury, In the Morphology window click Open… and select your
modified .cif file to visualize your new morphology

==VisualHabit==

The shape of a crystal results from the relative growth rates in different
directions. Strong intermolecular interactions, or synthons, in one direction, can
result in elongated crystal shapes like needles forming. Needle-shaped crystals
are common in pharmaceuticals and are undesirable due to their poor processing
characteristics. Being able to predict needle formation from a crystal structure is
helpful to understand potential manufacturing challenges.

1. Launch Mercury by clicking its icon. In the Structure Navigator toolbar,
type UREAXX to bring up the structure for urea.

2. Click on the CSD-Particle menu, select Morphology, then select VisualHabit…
3. In the VisualHabit dialogue box, you will see several options. On the left, you
will find options to change the calculation settings, such as which forcefield
is used and the limiting radius for the calculation. You can also choose
whether to add an electrostatic correction or not. On the right you will see
where the lattice energy results will appear once the calculation is complete.
For the purposes of this tutorial, we will keep the default options. These
typically work well for most situations, but if you know you are looking at
specific chemistry or a charged system, you may want to change these
settings.
4. Click the Calculate button to start.
5. The dialogue box will now update to show the results of the VisualHabit
calculation. The lattice energy results are shown in the section on the right in
kJ mol-1
. From here, you can see the total lattice energy as well as the
contributions from the electrostatic, van der Waals, and hydrogen bonding
energy terms. It’s clear from these results that the lattice energy for urea is
dominated by the hydrogen bonding energy in the crystal structure.
6. The convergence chart shows how the lattice energy changes over the course
of the calculation out to the limiting radius and gives an indication of whether
the calculation has converged successfully (indicated by the green tick at the
bottom of the chart). This chart tells us that the lattice energy comes close to
its final value in a small distance for this structure. Urea is a small molecule,
so this is what we would expect to see.
7. If we look at the Mercury visualizer, we will see that the calculated
morphology for urea is now shown. VisualHabit calculates an elongated
morphology for urea where the long axis is aligned to the polar axis of the
urea molecule.
8. We will now explore the reasons for this elongated shape by examining the
nature of the intermolecular interactions, or synthons, in more detail. Click
on the Synthons tab in the VisualHabit dialogue to change the information
that is shown.
9. The synthons that contribute to the lattice energy, along with the centroid-centroid
distance and component energy terms, are now shown. Click on the
Interaction Energy header (you may need to scroll along to see it) to sort this
column from the strongest interaction to the weakest. Once again, you will
see that the lattice energy for urea is dominated by a small number of strong
hydrogen bonding interactions.
10. Now let’s look at the two most important interactions. Click on one of the
rows in the table to highlight that interaction and show the synthon in the
Mercury visualizer. You can select multiple rows by holding down Ctrl and
clicking on the rows of interest. Holding down Shift and clicking will let you select
multiple rows at once. Select the top two interactions for UREAXX
(synthons 8 and 9).
11. You will see in the Mercury visualizer that two other urea molecules have
appeared above and below the central molecule. The red dashed lines
between the molecules highlight the synthon, and the value beside the line
shows the interaction energy. You can clearly see that the strongest
interaction in urea aligns with the fastest growth direction.
12. Click the Visualiser tab in the VisualHabit dialogue. From this tab you can
change the way that the morphology is displayed in Mercury, such as
changing the colour of the faces and the edges. You can also change how
synthons are displayed.
13. Click the radio dial in the Synthons section to display Distance rather than
Energy.
14. The Mercury visualizer will update to show the centroid-centroid distance of
the synthons in Å. These short, strong types of hydrogen bonds in the crystal
structure of urea are key to understanding its growth and the shape of its
crystals.

==Conclusion==
Crystal shape is governed by the relative growth rates in different directions.
Strong intermolecular interactions, or synthons, in one direction can result in
elongated morphologies. The crystal structure of urea is dominated by strong
hydrogen bonding interactions that occur in tapes that propagate along the
crystallographic c-axis. This results in an elongated morphology for urea.

You should now know how to calculate a morphology using VisualHabit for a
CSD structure in Mercury and how to visualize and explore the key interactions
in that structure relative to the calculated crystal shape.