EON
Electrostatic Similarity for Lead-hopping
EON is an electrostatics comparison program - it compares electrostatic potential maps of pre-aligned molecules and determines the Tanimoto measures for the comparison. As the electrostatic potential of molecules is not strongly linked to the molecular graph, EON can screen molecular databases for electrostatic similarity to a lead compound to identify lead-hops.
Since the input molecules must already be aligned, EON is suitable for analyzing the output structures from programs such as ROCS, thus yielding compounds with similar shape and electrostatics.
EON contributes significantly to lead generation and library design. In a recent study, Abbott scientists reported that EON's post-processing of ROCS hits helped them lead-hop a MCH-1 series that had demonstrated in vivo potency issues [1]. In a chemical genomics project directed toward antagonists for NAADP, EON was used in complement to ROCS to identify a low nanomolar binder to the NAADP receptor [2].
Two molecules from the MDDR with substantially different chemistry, but high shape and electrostatic similarity (Tshape > 0.75, Telectrostatic > 0.3).
Features
- Identifies molecules with high electrostatic similarity
- Reports rigorous Tanimoto measure between electrostatic grids
- Offers various charge models; user-defined models may also be used
- Integrates well with ROCS
- Distributed processing via PVM for most Unix platforms
For EON and All OpenEye Products
- Multiple file format handling: robust reading and specification-compliant writing of: SMILES, SLN, SDF, MOL, MOL2, PDB, FASTA, MOPAC, MacroModel, XYZ, CCP4, XPLOR, and OEBinary.
- Platform independence: support for Linux, Windows, Mac OS X and many flavors of Unix in both 32 and 64 bit.
[1] Muchmore, S., Souers, A. J., Akritopoulou-Zanze, I., Chem. Biol. Drug Des., 2006, 67, 174 DOI: 10.1111/j.1747-0285.2006.00341.x.
[2] Naylor, E., et. al., Nat. Chem. Biol. 2009, 5, 220 DOI:10.1038/nchembio.
