Faster insights and better science in the search for desperately needed new therapies

Sep 27, 2021 · By David Gosalvez, Ph.D.

The Increasing Importance of Biologics and Multidisciplinary Drug Discovery

During the last few years we’ve seen the increasing importance of biologics as therapeutic agents. According to an article, “The Ever Increasing Attraction of Biologics” published in Chemistry World, “Biologics are one of the fastest growing classes of therapeutic compounds, rapidly outpacing the growth of small-molecule drugs. By 2020, analysts are expecting biologics to make up over a quarter of the entire pharmaceutical market. This drive towards biologics is due to their ability to reach targets considered ‘undruggable’ using small-molecule therapies, and because of the benefits, or rather the reduced side-effects, offered to patients through better-targeted therapies.”

With this increasingly urgent drive to discover and develop novel bio therapeutics in areas such as oncology, it is crucial that researchers are equipped with the best possible tools to capture, manage and exploit all the available data. Traditionally, distinct software applications have been used to support chemical SAR and to analyze biological sequence-based SAR (bioSAR). With the growing adoption of multidisciplinary drug discovery teams, a unified chemistry/bio-sequence search and display application is critical.

In this post we drill into these requirements in more detail and discuss how an ideal bioSAR tool should support faster insights and better science in the search for desperately needed new therapies.

Researchers are struggling with a data deluge, and need effective tools to locate, extract, sift and filter relevant data for further detailed visualization and analysis. With biologics, these applications will need to understand and manage bio-sequences, and an immediate requirement will be to allow sequence searching, using a standard tool such as BLAST to search across internal and external sequence collections, to collect and import the appropriate hits in a standard format, and to link them to other pertinent properties (bioactivity, toxicity, physicochemical, DMPK, production, etc.)

With a tractable data set on hand, researchers will want to explore sequences to try to discern particular motifs or sequence differences that are correlated with bioactivity or desired physicochemical or DMPK profiles, and thus potentially amenable to further manipulation and enhancement.

The sequences must be aligned, for example by CLUSTAL Omega, and visualizations should present sequences so that sequence differences are immediately highlighted, and monomer substitutions can be explored for potential links to bio-therapeutic activity. LOGO plots to investigate the distribution of monomers in a set of sequences, and annotations to highlight and share areas of interest will also help researchers to get to insights more quickly.

If scientists want a deeper dive into the underlying structure of the sequence or a region, immediate access to a detailed and interactive 3D rendering of the biomolecule’s structure can provide a different lens through which to understand how different monomers substitutions may impact protein folding or active site binding and thus activity.

There may also be cases where required specialized analysis or visualization capabilities are only available in a separate in-house developed, third party, or open-source application, and the provision of an extensible Web Services framework will enable these to be quickly linked in to an enhanced analysis pipeline that can then be shared with colleagues and collaborators.

A bioSAR system providing the capabilities discussed above, equipped with an intuitive and unified user interface catering for novice and power users alike will enable them to derive faster incisive insights and make better informed scientific decisions in the search for novel bio therapeutic agents targeting some of the world’s most pressing unmet clinical needs.

With our Lead Discovery Premium solution, scientists can analyze and visualize chemical structure & biological sequence data, compare, score, and segment leads based on data-driven multi-parametric optimization. Whether you are a scientist working in drug discovery or materials science, you can discern and understand the trends and outliers in your data to ensure a successful candidate selection and promotion strategy.

Lead Discovery Premium combines the analytics power of TIBCO® Spotfire® with the chemical smarts PerkinElmer is known for, then adds powerful biological sequence intelligence to create the premier platform for scientific visualization and analysis. The guided workflows empower you with the ability to find and assemble any data you want to answer any scientific question – from drug discovery to materials science experiments – in minutes rather than days, independent of your IT department. Read more about our Lead Discovery Premium here.

To learn more about Lead Discovery Premium, and how we support a range of small molecule R&D and large molecule R&D customers, read more here. You can learn more about the extensive list of differentiating capabilities in our Lead Discovery data sheet with reference videos below:

Sequence Analysis window that enables motif discover and activity assessment with an integrated workflow.

The open and extensible web services framework that allow BLAST and CLUSTAL alignment out of the box.

The ability to view sequence information directly in line with activity data, including the ability to view differences relative to a reference sequence and correct handling of gapped annotations.

The elegant support for import of various biological sequence file formats.

About the Author

David Gosalvez, Ph.D., has over 20 years of experience building software platforms and solutions for the chemical and pharmaceutical industry. He is currently responsible for product strategy and business development for PerkinElmer Informatics Signals research and clinical platforms.