My name is John Van Drie and today I'm going to
be discussing pharmacophore methods in drug discovery.
I am currently an independent consultant based in the Boston area.
My company is Van Drie Research and I've been active in this area for over 30 years.
I've worked for major pharmaceutical companies,
helped to start a small biotech company,
and now mainly work with small biotech companies in drug discovery.
In slide 2, I highlight the outline of what I would like to discuss today.
I'll begin by talking about three classes of
drug targets and where pharmacophore methods can play a role.
Next, I will give some basic definitions.
Thirdly, I will discuss the role of pharmacophores in drug discovery.
Then I will give an example of a workflow of pharmacophore-based virtual screening.
Next, I will describe the process of pharmacophore discovery,
how we move from a structure activity relationship to discover a pharmacophore.
Then finally, I'll point you to some resources that will
let you do these type of calculations at home.
To begin, it's important to have an answer to the question:
what is a pharmacophore?
The answer is:
it is a spatial pattern of functional groups essential for biological activity.
This is a pattern that emerges from a set of molecules and their biological activities,
in other words, a structure-activity relationship (SAR).
One of the key points to note in this definition is that this is a 3D thing.
'Spatial' refers to three dimensions and the functional groups are things on the molecules,
a very important aspect is that the presence of
these functional groups are essential for biological activity.
In general, when they are not there,
you will not see biological activity.
We'll see more examples of this and this will become clearer.
Why do we need pharmacophores?
I will show you some examples of how we can discover
novel chemical starting points by
virtual screening to jumpstart a drug discovery process.
Next, we can use pharmacophores to drive
iterative molecular design, usually in
those cases where no structure of the drug target is available.
Again, I will give you an example of that.
One can think of three classes of drug targets.