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Why Do Conformational Searches?
The 3-dimensional structure of a molecule helps determine its
properties. The importance of understanding 3-dimensional structures
has made molecular graphics programs, like Chem3DTM, the most widely used type of chemistry calculation program.
While all molecular graphics programs display 3-dimensional structures,
the results you get from using a molecular graphics program are
only as good as the structures you view. You still need to be
sure that the structures viewed are the ones that determine the
molecule's properties.
As chemistry students learn very early on, the typical molecule
has many possible conformations, but only a few of them contribute
significantly to it's experimental properties. Conformational
search programs systematically search through the possible conformations
of a molecule to find the low energy conformations - the ones
that determine a molecule's properties. It takes days or weeks
of costly lab work to identify these conformations experimentally,
a task that a conformational search program running on a desktop
computer can often do in only a few hours.
Despite the fact that all molecular graphics programs have minimizers,
chemists still need a conformational search program. A minimizer
finds the lowest energy structure of the conformation you started
with; it cannot tell you if there are other, lower energy conformations.
This makes the right conformational search program a very useful
tool.
Chemists most frequently use conformational searches for finding
the global minimum since the lowest energy structure is the structure
that occurs most often in a sample of the molecule. However, the
global minimum often is not the only important conformation of
a molecule. The statistical average of all conformations (also
called the ensemble average) determines the experimental properties
of a molecule. All low energy conformations contribute significantly
to this average. In addition, when you are working with biologically
active molecules, the global minimum is not necessarily the conformation
that is responsible for activity. When running chemical reactions,
other conformations may react faster than the global minimum or
produce different products.
When working with related molecules
So far we have focused on the benefits of conformational searching
when dealing with individual molecules. However, chemists often
work with sets of related of molecules, that is, where all the
molecules in the set have one or more features, or substructures,
in common. When working with related molecules, chemists are interested
in understanding the reasons for variations in the properties
of the molecules in the set. Changes in the conformational preferences
can greatly contribute to these variations. For example, if a
modification changes the conformation responsible for biological
activity from a low-energy structure to a high-energy one, the
activity will be reduced, even if the molecule is more active
once it is in the active conformation.
Conformational search programs are useful for determining whether
conformational changes contribute to property differences among
related molecules. In order for you to determine whether conformational
preferences have changed, you must search through all the conformations
of all the related molecules you are working with and then determine
which conformations are equivalent. Conformations in different
molecules are equivalent when the torsional angles in the common
substructure are about the same. Once you have identified the
equivalent conformations, you compare their conformational energies.
If they are different, it means that conformational preferences
have changed. Doing this by hand can be very tedious. Thus, it
is highly desirable to have a program that does this for you.
ConformerTM, will enable you to not only identify the global minimum, but
also to identify all conformations that contribute significantly
to the experimental properties. An important feature of the program
will be functionality that makes it easy to determine how modifications
to a molecule affect its conformational properties. Conformer
will be an add-on module to Chem3DTMTM and will work as if it were an integrated part of it. Conformer's
Advanced Analysis tools make it easier for you to determine how modifying a molecule
affects its conformations.
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