1. Overview

Small molecule conformer generation is a hard problem. Very small molecules like acetone and ethane are not tremendously challenging. Add only a few more atoms to the simplest organic molecules and conformer generation becomes factorially more problematic. Models used for gas-phase conformer generation are inherently inaccurate. Model quality is further degraded by attempting to incorporate something of the solution phase or protein bound conformational preferences. The latter is made especially difficult when the structure of the macromolecule to which the small molecules may bind has not been determined. Yet these are exercises routinely performed using conformer generation software. Inaccurate models and incomplete information are coupled to conformer generation engines that attempt to approach the intractibly large search space of shapes that small molecules might adopt. A modicum of hubris is required to undertake such a task, and further expect it to be useful.

Molecular modelling results routinely depend on the quality of conformers directed into a workflow upon which results are rationalized and predictions are made. Prior to version 2.0, Omega was designed primarily to support high throughput virtual screening exercises. Reproducing bioactive conformations was formerly the focus of the program to the exclusion of all other possible exercises. A number of changes have been introduced in Omega version 2.0 that make it a more general purpose conformer generation program. Higher quality force fields (MMFF and derivatives) replace the Dreiding force field. User defined selection of the force field is possible, providing a means of biasing searches toward conformations with particular attributes. 3D model construction has been redesigned to capture non-idealized bond angle geometries while maintaining a level of symmetry appropriate for rotatable bond searches. Ring conformer generation has been made exhaustive within the limits of a force field and optimizer's ability to identify local minima. With the new features in version 2.0, Omega is a more suitable tool for low throughput conformational analysis. In addition, high throughput conformer generation and the ability to reproduce bioactive conformations has improved as a result of the additional features.

				OMEGA C++ Toolkit

				OMEGA C++ Toolkit