ReFlex3D: Refined Flexible Alignment of Molecules Using Shape and Electrostatics

We present an algorithm,
ReFlex3D, for the refinement of flexible
molecular alignments based on their three-dimensional shape and electrostatic
properties. The algorithm is designed to be used with fast conformer
generators to refine an initial overlay between two molecules and
thus to obtain improved overlaps as judged by an increase in calculated
similarity values. ReFlex3D is open-source and built as a python package
working in combination with the OEChem Toolkit. As such it can readily
be implemented in existing workflows ranging from the selection of
compounds from a virtual screening campaign to the construction of
similarity based prediction models to estimate binding affinities.
We evaluate ReFlex3D against the AstraZeneca Validation Test Set and
illustrate its potential within a predictive model compared to an
established method (Posit).