Great Science Makes a Great Consulting Project

Previously I’ve discussed the trend to outsource computational chemistry and great people. In this third post I talk about great science being one of the key factors to a great consulting project.

Cresset consultants always use the best software for the job at hand and we do not restrict ourselves to using only Cresset’s software. Having said that, clients often come to us for consultancy projects because of the innovative software we offer, underpinned by proven scientific methods.

What makes Cresset’s scientific software offering unique is field technology, a patented set of algorithms that describes molecules based on their biological activity. The resulting field point descriptors of molecules give a powerful basis for analyzing and comparing molecules using biological activity rather than chemical similarity (see Figure 1, below).

2D structures of structurally diverse bioisosteres both active at PDE3, cAMP (the natural substrate) and SKF93741. The field patterns of the compounds reveal that they are biologically similar.

fields_example
Figure 1: Closing the gap between chemistry and biology: two structurally diverse molecules with similar biological activity.
Above left: 2D structures of structurally diverse bioisosteres both active at PDE3, cAMP (the natural substrate) and SKF93741, a PDE3 inhibitor.
Above right: The field patterns of the compounds reveal that they are biologically identical and share the same activity.

Clients come to us with many different starting points for projects. Because Cresset’s technology can work with or without a structure of the target protein it can be used on the widest range of target classes. This also makes it easy to start a consulting project when the structure of the target protein is not known.

For example, you may have an active compound that is unusable due to off target activity or patent conflicts. Therefore, your goal is to modify this compound to avoid the undesirable effects while keeping the biology the same. We can characterize the molecule according to its field activity then look for compounds with new chemistry that have the same activity – often from a different structural class.

A client may wish to find an inhibitor for a natural substrate or peptide. Our team will use our software to mimic the chemical properties of the recognition sequence in order to find a small molecule inhibitor. We’ve also worked on projects where the starting point has been anti-bodies or large protein-protein interactions, but these are much harder to deal with computationally.

The case study Virtual Screening with 11βHSD-1 is an example of a virtual screening project Cresset worked on, that demonstrates the validity of Cresset’s field based approach.

All posts in this series:



Dr Martin Slater,
Director of Consulting Services