Multiple molecular superpositioning as an effective tool for virtual database screening

Molecular superpositioning is an important task in rational drug design. Us ually it is the key step in a comparative analysis of molecules by 3D QSAR methods. Also it is helpful for the elucidation of a pharmacophore and cruc ial in the attempt to derive a receptor model. Generally speaking, molecula r superpositioning can be seen as the analog of molecular docking if the re ceptor structure is not available, and direct methods are not applicable. V irtual database screening is the computational counterpart to modern experi mental techniques like high throughput screening and assaying of combinator ial libraries. Both screening techniques have the common goal to detect act ive molecules in a large selection of compounds. Usually hundreds of thousa nds of candidates are to be tested, hence, time is the limiting factor and rapid processing of utmost importance. Descriptor-based methods that usuall y provide a simple linear encoding of the molecules meet the demands of com putational speed and have been used predominantly for the task of virtual s creening, for a long time. However, more powerful superposition methods hav e been developed during the past few years and now begin also to be applica ble to screening large databases. Especially in combination with the faster methods, molecular superpositioning as the final step of a filtering proto col provides a powerful tool for virtual database screening. The present wo rk reports on our latest developments of molecular superpositioning techniq ues and assessing their applicability to virtual database screening.