This site is maintained by John H. Van Drie, as an open-source resource for all things related to pharmacophores.

Open-source pharmacophore-based 3D Database searching

Rajarshi Guha (Indiana University) and I have recently made available as open-source some pharmacophore search software. Look at Rajarshi's page to download that Java software, and get some cryptic documentation. Contact me for more info. This is brand-new, and is evolving, but it seems to work. It's all command-line driven at the moment, and functions a lot like the old ALADDIN code (Van Drie, Weininger & Martin, JCAMD, 1989, 3:255). This new open-source stuff is based on the open-source Chemistry Development Kit (CDK).

Building 3D databases with public or open-source software

A number of options are now available beyond the offerings from the commercial vendors:

Note too that PubChem is now available in 3D format, PubChem3D and available for download.

Pharmacophore discovery

These methodologies are also called 'pharmacophore identification', 'pharmacophore perception', or 'receptor mapping'. The first commercial software for pharmacophore discovery was the Catalyst software, of which I was one of the co-authors. (DISCO is often cited as the first, but that appeared from Abbott only after they'd seen initial versions of Catalyst. DISCO did indeed appear in the literature before Catalyst). Catalyst's approach to pharmacophore discovery has numerous weaknesses, which I've addressed in my latest work on pharmacophore discovery, DANTE, which is described in the following papers.
I recently published a review in Curr Pharm Design, 2003, 9(20):1649, and also have a book chapter reviewing pharmacophore discovery: Computational Medicinal Chemistry and Drug Discovery, Tollenaere Bultinck de Winter and Langenaeker (eds.), NY: Dekker.

Here is a script and a small C program which one can use with the commercial Catalyst software to implement the Mayer et al method, the algorithm at the heart of DANTE:

Frequently-asked questions (FAQ's) about the practical issues of constructing pharmacophores

There is a tremendous amount of confusion surrounding many issues surrounding pharmacophores and their use. I would like to clarify some of these here. Many thanks to Helene Decornez of AMRI for constructing an initial list of questions, which formed the basis for these FAQ's. During my time at Abbott (where I developed ALADDIN, the progenitor to all pharmacophore search systems), at BioCAD (where we developed Catalyst, now marketed by Accelrys), and at Upjohn, I probably built over one hundred pharmacophores, and have learned a number of practical tips on how to build and use pharmacophores.
Twenty years ago, one built pharmacophores manually, and many of these were good pharmacophores (see the first 5 volumes of JCAMD for such examples). Now, people mainly rely on the low-quality automated pharmacophore generation tools commercially available; as a result, almost an entire generation of CADD scientists have never even seen a good pharmacophore.
  • Who was the originator of the concept of a pharmacophore, and when did this occur?
    3D database searching

    I developed the ALADDIN software, collaborating with Yvonne Martin at Abbott Labs. That pioneered a new approach to 3D database searching, and was used in the first success for virtual screening, the discovery of a novel template for D1 agonists.
    Link to PubMed citations

    Contact me

    Those interested in anything related to matters above: send me an e-mail and let's initiate a dialogue.

    Definition of the term pharmacophore

    The material that was here for many years has now been moved to a refereed journal, in a 2007
    article by me in the IEJMD, an issue dedicated to Monty Kier.