XedeX

conformation hunting with the XED force field

Evaluate XedeX™for one month free of charge

XedeX™ (the XED eXplorer) is a fast and flexible conformation hunting tool. Unlike most other fast conformational analysis programs, XedeX™ is not rule-based: every conformation is generated and fully minimised by the XED force field. The conformation hunting algorithm is optimised for rapid exploration of the conformational space of drug-like molecules, generating a small, diverse and representative set of conformations. XedeX™ has been shown to perform well against other commercially-available conformational analysis packages, and has also been extensively validated through its use in the FieldScreen™ field-based virtual screening system.

Features

Reads/writes molecules in SDF or mol2 format
Efficient pop-to-3D for 2D input molecules
Fast molecular dynamics for exploring ring conformations
Monte Carlo bond twist routine for conformation generation
Fast torsion pre-minimisation for speed
Uses the XED force field for improved conformational accuracy
Conformation generation biased towards efficient sampling of conformational space
Fast, with all conformations properly minimised

New feature: XedeX™ now has extra options to reduce the problem of hydrophobic collapse in long, flexible molecules. This significantly improves the quality of conformations for these compounds.

XedeX™ is currently available as a flexible Linux command line tool.

Analysis of Conformational Searching Protocols

We have compared XedeX™ to other conformation hunters following J. Bostrom (JCAMD 15 1137-1152, 2001). 32 molecules for which an accurate binding conformation is known are subjected to a conformational search starting from a 2D structure. The RMS difference between the bound conformation and the closest conformation found by the conformational search program is then measured.

Method	<0.25	0.25-0.5	0.5-0.75	0.75-1.0	>1.0
Catalyst	6	10	3	9	4
Confort 1	4	7	4	6	11
Confort 2	2	4	6	5	15
Flo99	5	15	5	4	3
MMFF94S	5	9	6	4	8
MMFF94S GB/SA	10	9	6	6	1
AMBER*	4	16	1	3	8
AMBER* GB/SA	6	16	2	4	4
OMEGA	2	11	8	4	7
XedeX (fast)	6	11	7	2	6
XedeX (default)	9	10	6	3	4
XedeX (optimal)	10	13	2	3	4

The XedeX (fast) results are for the XedeX™ software as used in the FieldScreen™ package, where options to improve speed at the expense of completeness are chosen. Note that the XedeX (fast) results are limited to only 50 conformations, while the XedeX (default) results are limited to 100 conformations. The other conformation hunting tools were less constrained.

As can be seen, the XedeX™ protocol performs very well compared to other known conformation-generating methods. Indeed, using the generally accepted criterion for 'correct' (0.5A RMS), the optimal settings for XedeX get 23 of the 32 compounds correct; more than any other method. The only methods which perform comparably (MMFF94S GB/SA and AMBER* GB/SA) involve exhaustive Monte-Carlo searches with a full solvation model in Macromodel, produce (potentially) thousands of conformations for the large molecules, and take roughly 10 CPU-hours to complete on the 32-compound set. XedeX™, by comparison, takes less than 10 CPU-min in 'fast' mode.