Brian Cole of OpenEye Scientific Software
OpenEye is a software company in the field of molecular modeling that sells software into the pharmaceutical research industry. The company was founded on fast software and has invested heavily in achieving that vision. OpenEye was also founded on the vision of portable software using open standards, making OpenCL a natural fit.
FastROCS is an extremely fast shape comparison application, based on the idea that molecules have similar shape if their volumes overlay well and any volume mismatch is a measure of dissimilarity. It uses a smooth Gaussian function to represent the molecular volume, so it is possible to routinely minimize to the best global match.
The unprecedented speed of FastROCS represents a paradigm shift in the potential for 3D shape screening as part of the drug discovery process. Now, in just seconds, FastROCS can perform a virtual screen over an entire multi-conformer representation of a corporate collection to find active compounds with similar shape to a lead compound (a task that could previously take up to a day). Recent work suggests that the underlying ligand-based shape similarity approach is competitive with, and often superior to, structure-based approaches in virtual screening, both in terms of overall performance and consistency.
In addition to revolutionizing the capabilities of virtual screening and lead hopping, FastROCS opens the door to performing NxN shape comparisons over an entire multiconformer database. This ability makes 3D shape clustering of large databases a practical possibility for the first time.
FastROCS alignments have a number of additional applications including: 3D QSAR, SAR analysis, understanding of scaffold diversity and detection of common binding elements. Alignments to crystallographic conformations have also been useful in pose prediction in the absence of a protein structure.