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<h2>Adding Points to the Pharmacophore</h2>
This program allows you to explore the effects of adding features to the
pharmacophore in your P3D file in a straightforward manner.
<h3>Selecting Atoms</h3>
The first step in adding features to the pharmacophore is to select
atoms in PyMol that define the feature(s). For single-atom features,
such as hydrogen-bond donors, you should select that atom; for
multi-atom features, such as aromatic groups, you should select one of
the aromatic atoms.
<p>After selecting the atoms, click the <tt>Grab Atoms From PyMol</tt>
button at the top of the <tt>Alignment Criteria</tt> page. The new
atoms are added at the end of the list of atoms already in the
pharmacophore:
<center><img src="AddPoints-shot1.jpg"> </center>
By clicking the <tt>Highlight</tt> button next to the feature
assignment box for each feature, you can highlight the corresponding
atom in the molecular sketch (this is the gray circle in the figure above).
<h3>Assigning Feature Types</h3>
<p> To assign a feature type, click the feature assignment box for
each new feature and select the appropriate type. The program will only
show you feature types that match the atom you selected:
<center><img src="AddPoints-shot2.jpg"> </center>
For example, in the illustration above, atom 3 is involved in three
different feature types, you must select one for the pharmacophore.
<h3>Defining Distances</h3>
After assigning types to the points you added, the last step in
updating the pharmacophore is to set the distances between the new
feature(s) and the others in the pharmacophore. This is done by
clicking the <tt>Grab Distances</tt> button.
<p>When <tt>Grab Distances</tt> is pressed, the software examines
reference molecule, calculates the distances between the new features
and those already present in the pharmacophore, and adds the new
distances to the list of distances at the bottom of the window:
<center><img src="AddPoints-shot3.jpg"> </center>
The distance ranges are automatically calculated based on a tolerance
value.
<p>Note that the sketch of the pharmacophore on the molecule has also
been updated to highlight the atoms in the new feature (drawn with red circles in
the sketch).
<h3>Exploring Changes</h3>
Once the new pharmacophore has been defined, you can switch back to
the <tt>Search Results</tt> tab in order to explore how your current
set of molecules can align.
<p><b>Note:</b> Defining a new pharmacophore will destroy any
alignments that you may have found to the current pharmacophore. If
you would like to save these, you should <a
href="SavingResults.htm">Save your work</a> before clicking <tt>Grab Distances</tt>.
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