Pharmacophore modeling software

One of the early examples of pharmacophore modeling of the ala- and aib-AR subtypes was carried out by means of the Apex-3D software [100]. The common features of the pharmacophore models of the two arAR subtypes were a protonated amine, an aromatic ring and a polar region. The main difference between the two pharmacophores was the distance between the aromatic ring and the amine function. 

In 1982 Ayerst Laboratories in Montreal became the first company in Canada to install a commercial software tool (the SYBYL suite from Tripos Associates) to help in the development of pharmacophoric models from structure-activity relationships. The installation of the software was the second ever, worldwide, by a company and is a testimonial to the foresight of the director of medicinal chemistry, Dr. Leslie Humber, for having championed its installation. Dr. Adi M. Treasurywala, then an organic chemist with some experience in medicinal chemistry, became the first industrial computational chemist in Canada that year. The use of modeling approaches contributed in a minor but significant way to the discovery of the compound known as Tolrestat, which was an inhibitor of lens aldose reductase. This led to the acknowledgment of Treasurywala as a coinventor of the drug on several patents that were filed in this research area. Approximately in 1983, Ayerst closed down its discovery effort in Canada and moved to Princeton, New Jersey, where an expanded effort in the area of computational chemistry continues. 

At the beginning of this chapter we will look into the different automated alignment methods as correct alignment is the first and most important prerequisite for a successful pharmacophore identification process. Further, we will elaborate how essential issues of pharmacophore modeling such as conformational search, pharmacophore feature definitions, compounds structure storage and screening are handled by various available software packages. 

Pharmacophore Model Generation Software Tools GASP... 

In this chapter, we have tried to demonstrate the great diversity of software tools available to the researcher in the area of ligand-based pharmacophore modeling. With the expansion of combinatorial chemistry techniques and the need to manipulate very large amounts of real or virtual chemical data, pharmacophore-... 

Selecting chemical feature types for the construction of pharmacophores is the most important step towards pharmacophore creation. In early pharmacophore modeling techniques such as the active analog approach described by Marshall et al. [34], pharmacophore features could contain any fragment or atom type. Later techniques such as the software package Catalyst [35], however, use a... 

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