Ligand-based virtual screening as a service

“Above and beyond the physical data output, it is often the insight that is gained from the project that is the most useful deliverable.”

Cresset Consulting has been providing modeling and computational chemistry support for drug discovery projects for over a decade. We have collaborated with academics, biotechs and big pharma offering a unique blend of bespoke molecular modeling expertise and state of the art field-based modeling technology.

Over this time we have naturally covered a wide range of therapeutically relevant drug targets and also many disease areas in which the biological target was unknown. The majority of these projects have involved ligand focused virtual screening, which is the mainstay of our consulting business.

There are several reasons why our virtual screening service is so popular:

• It is an effective means of switching chemical series to identify new intellectual property
• It is a fast and cost effective way of testing several different hypotheses
• Our common sense approach means we set realistic expectations of what can be delivered
• The chemical understanding gained from our collaborative working model goes beyond the physical project results to add valuable insight to your research.

Switching Chemical Series to Find Clear IP

Intellectual property (IP) space is of paramount importance in drug discovery. It is increasingly difficult to find valid and useful protein targets for which drugs can be marketed. Consequently, many of the good biological targets are quickly saturated once they are identified. Virtual screening offers a highly efficient and rapid process for hopping from one chemical series to another, which is an effective way to find new chemical space without IP restrictions.

The Blaze ligand-based virtual screening software uses the electrostatics and shape character of known ligands to search large chemical collections for molecules with similar properties. This makes it possible to identify new chemical series and, therefore, exploit the narrow windows of opportunity afforded by IP constraints.

Field-based similarity searching of molecules is a 3D method that accurately encodes surface electrostatics and shape. It is consequently largely independent of the underlying molecular framework. The method is optimized for finding the combination of features which are more biologically relevant to the protein interaction than are present in the chemical structure itself.

A Cost Effective Way of Testing Several Hypotheses

Virtual screening approaches are vastly faster and cheaper to conduct than their traditional wet chemistry and biology equivalents. Millions of commercially accessible compounds can be run through a virtual screen in a matter of days on our moderately sized CPU cluster. An equivalent high throughput screen could cost in the order of $2m.

One clear advantage of the speed and cost of virtual screening is that several hypotheses can be tested using virtual screening. Only one hypothesis needs to provide a useful output for this cost effectiveness to be realized.

Common Sense and Integrity Mean Realistic Expectations

Claiming that virtual screening is always the answer is quite rightly met with disdain from seasoned medicinal chemists, many of whom at some point have been naively promised something which in reality could not be delivered by modeling. The cost effectiveness provided through computational chemistry is only realizable if something of value is delivered to the drug discovery program, and delivered in a timeframe in which it can be usefully employed.

In Cresset’s consulting projects we strive for a deeper understanding of each specific project and aim to offer the solution that we believe will provide the best chance of success. No modeling computational techniques have a 100% success rate, but our experience will help drive the chance of success as high as possible with our recommendations for that specific task.

If our experience and investigations suggest that we will not get meaningful results through virtual screening then we may suggest a more suitable course of action, including not doing the task! We bring common sense to all of our projects, informed by our integrity and our scientific expertise.

Delivering Chemical Insight Along with Physical Results

Cresset consulting provides a truly consultative service. By that we mean that we listen carefully to our clients throughout the project, questioning them to identify their needs and goals as clearly as possible, and working closely with them as the project progresses. This collaborative approach means that both parties gain far more scientific insight from the relationship than a simple set of virtual screening results.

We take great care in providing the results in whatever way is most helpful to our clients. We provide a variety of output files held privately and securely for each client on our FTP server. The output is frequently SDF files, PowerPoint presentations or document files, which can be full written reports if specified.

Above and beyond this physical data output, it is often the insight that is gained from the piece of work that is the most useful deliverable. Post project wind-up meetings, either face-to-face if possible or via the web, have proven particularly valuable to our clients over the years.

Find out more about Cresset’s consulting services and virtual screening, or contact us to find out how we can add value to your projects.

Dr Martin Slater,
Director of Consulting