Mining free compound databases to identify candidates selected by virtual screening

Abstract

Background: The search for effective ways to discover new and better chemical probes to explore basic biology is never ending. With the advent of genomics and proteomics, data are rapidly accumulating on the role of several proteins and their implications in cellular function. However, the accumulation of knowledge on new proteins is not reciprocated at the level of new chemical probes that would help us understand protein function by modulating it. An emerging solution is virtual screening in which millions of molecules are evaluated with computers rapidly and cheaply relative to high-throughput screening. Objective/method: In this perspective we will use our experience to illustrate how small, modestly funded laboratories can use virtual screening successfully to develop chemical probes. The chief contributors to make this possible are the availability of free databases containing purchasable compounds and powerful and accessible software. Conclusion: That virtual screening can be used to find chemical probes is a reality. Unfortunately, groups that would benefit most from this powerful technique underuse it. Making biologists aware of the existence or capability of virtual screening will greatly speed the identification of new chemical probes.

Keywords::

• calcium
• chemical probe
• in silico
• ligand-based
• NAADP
• second messenger
• shape-based
• virtual screening

Acknowledgement

We thank OpenEye for the generous use of their software and their commitment to seeding basic science.

Notes