11. Crystal Clear: Unveiling the Secrets of Crystallography and Drug Design

In our next episode, we’re joined by Jason Cole, a Senior Research Fellow at the Cambridge Crystallographic Data Center (CCDC). He shares his fascinating journey, starting from his childhood in Italy, where his love for science blossomed, all the way to his impressive career in computational chemistry and crystallography. We chat about what CCDC does in terms of gathering and sharing crystallographic data, the ups and downs of software development in this field, and why it’s so crucial to validate docking software. Jason also highlights the importance of data standards, the philanthropic mission of CCDC, and what the future holds for drug discovery, particularly with the exciting possibilities of artificial intelligence (AI) and quantum computing. It’s a great conversation packed with insights!

In our first episode of 2025, our hosts, Chris Williams and Dave Thompson, have the pleasure of speaking to Fernando Garces, CEO and co-founder of BioGlyph. Leading us from the sunny climes of Portugal through the tropical paradise that is London, on route to the West Coast of the US and A, Fernando shares his evolving love of science through the heights of academia, into industry, and now as CEO of a software company he co-founded to improve the modeling of complex multispecifics. Important questions are unpacked throughout - is London really a tropical paradise? How long can we keep milking podcast episode titles that take advantage of the homophonic property of pharma and farm? Oh, and we have another surprising guest answer to the ‘Deschênes Dilemma’… It is not to quote G. K. Chesterton, a proper nailbiter!

In our final episode of 2024, host Chris Williams and guest co-host, Under the Surface Executive Producer and CCG Vice President, Alain Deschênes have a long overdue chat with computational drug discovery rock star Rebecca Swett. Rebecca shares her journey from her academic beginnings to her current role at X-Chem, via roles at Novartis, Vertex, and Relay. Rebecca’s wide-ranging experience shines through as the conversation wends its way through cutting-edge computational chemistry covering machine learning, molecular dynamics, and DNA-encoded libraries. At the scale Rebecca works at, automation is key, so this topic comes up too. We’re not going to lie; it’s a lot. And, of course, there’s more … Rebecca highlights the significance of allyship and representation for women in science, and the role of community (with a shout-out to the long-running BAGIM modeling forum). Also, in the inaugural asking of the ‘Deschênes Dilemma,’ we find out what Rebecca would be doing if she wasn’t doing all of the above …   

On episode 8 of Under the Surface, we’re joined by The Molecular Assassin, Arijit Basu. Arijit describes his journey from India to the US via a transformative sabbatical in Israel. Landing in the Langer lab at MIT and then finding his industrial legs, Arijit turns to computational toxicology as a way to ensure that drug hunters enable the concept of Safety by Design as a core tenant for how they’re navigating chemical space. He doesn’t discuss how he got his cool nickname though, so if that’s what you’re after, you will be out of luck. This episode was recorded live in Montreal at our 2024 UGM.

This next episode of Under the Surface has us speaking to crystallographer Eric Larson. In episode 7, as you’ll hear, Eric’s a little nervous about having his thoughts committed to ‘perpetuity.’ But, as you’ll also hear, he does a great job. As our first second structural biologist on the show, he tells us about how he got into the field, the very real logistical challenges of working in industry, and his evocative description of what it feels like to peek ‘behind the veil’ and be the first on the planet to observe the structure of a previously unknown protein. It’s a magical episode This episode was recorded live in Montreal at our 2024 UGM.

Check out the next episode of our podcast, Under the Surface! In episode 6, Revolutionizing Nanoscale Visualization, we talk to Nanome CEO and co-founder Steve McCloskey. In a virtual rollercoaster of a conversation, he shares Nanome’s scrappy beginnings, the challenge and excitement of bringing new ways of interacting with models to the science community, and paints a vivid picture of an exciting element of the future of molecular modeling.  It’s Reality Jim, but not as we know it… Interested in giving this a test drive?  Contact [email protected] to set up a demo with Nanome.

In episode 5, Farm to Pharma, we talk to Dr. Dan McKay about his career in the pharmaceutical industry (he grew up on a Farm! See what we did there … ?). As a pioneer in the applied use of quantum mechanics, Dan describes his break into the industry from academia, his realization of the critical importance of water in understanding ‘what’s going on’, and offers some pointed observations on the applicability of artificial intelligence and machine learning in drug discovery. Throughout our time with him, Dan’s stories paint a vivid and exciting picture of what it means to support a modern discovery effort. Also, in a first for Under the Surface, we ask something of you, our audience. Can you help us, help Dan?

Welcome to the last episode of the year for our podcast, Under the Surface! In this episode, A CHRIStmas Carol, we conjure up some jovial spirits of the past as our Super Senior co-host Dave grills his colleagues on the founding, early years, and development of the Chemical Computing Group. As you’ll hear, Dave manages to make Research Group Leader, Anna Lin, and his regular co-host, Chris Williams, feel deeply uncomfortable and encourages them to step out of their inherent Canadian humility and embrace the fact that they contributed to the building of a thing that is still going strong - 30 years on! Reminiscences are shared, the field is reflected upon, and famous Canadians are listed. It is, dear listener, a roller coaster of an emotional ride.  

In episode 3, Instructions for a Life in Science, we talk to Dr. Vanita Sood about her experiences as a drug hunter. Vanita candidly shares her career journey, reflecting back on the choices she made, the opportunities and challenges she navigated, and the transformational science she drove.  She describes her recent transition from a large pharma company to a startup environment and the critical considerations she’s had to deal with. Throughout we talk about AI in discovery, the science of serendipity, and Mary Oliver the naturist and poet. Vanita expounds the spirit of paying attention, being astonished, and sharing this enthusiasm with others.. Strap in folks. Takeaways: Dr. Vanita Sood has 15 years of experience in drug discovery. AI in drug discovery has shifted from skepticism to enthusiasm. Switching fields can provide new perspectives and opportunities. Drug discovery requires teamwork and collaboration. Building connections in academia can lead to industry opportunities. The patient-centric approach drives drug discovery priorities. Data generation for AI needs to be consistent and relevant. Human insight is essential for interpreting complex biological data. Exploring new chemical spaces is crucial for innovation. Serendipity can lead to unexpected breakthroughs in research. Relying on machine learning for drug discovery raises concerns about data complexity. The best drug discoveries often come from unexpected patterns in data. Documentation in pharma is generally better than in academia, but still has gaps. Machine learning models need interpretability to ensure reliability and understanding. Transitioning from a large pharma environment to a startup presents unique learning opportunities. Collaboration in the pharma industry fosters a collegial environment despite competitive pressures. Terminated projects can provide valuable data for machine learning models. Attention to detail is crucial in scientific discovery and data curation. Balancing deep expertise with a general understanding of other disciplines is essential in drug discovery. AI and machine learning are transforming the landscape of drug discovery, requiring new skill sets.

Check out the next episode of our podcast, Under the Surface! In episode 2, Fun with Pharmacophores, we talk to Dr. Scott Rowland about pharmacophore-based techniques and their role in understanding receptor–ligand interactions, and ultimately, how they contribute to the design of new drugs. Recently retired, following decades in the pharmaceutical industry, Scott tells us about his journey through the field and his deep appreciation for collaborative science. Scott hasn’t completely hung up his abacus just yet though, and he tells us about his recent consultative adventures too! How have we managed to fit all of this in one episode? It’s a mystery. Takeaways: Dr. Scott Rowland has over 20 years of experience in drug discovery. Structure-based drug design is now widely accepted but still has untapped potential. Collaboration between medicinal chemists and computational chemists is crucial for success. 3D structures provide valuable insights for drug design. Team dynamics play a significant role in the drug discovery process. Consulting allows for flexibility and creativity in biotech startups. Pharmacophores are essential for understanding drug interactions. The concept of pharmacophores is evolving and is not static. Pharmacophore efficiency could be a new metric in drug design. The future of drug discovery relies on collaboration and innovative thinking.