On Drug Design

On Drug Design

"About the blog"

Personal reflections on drug design. Research interest includes combining new technology, informatics and science in innovative ways to tackle the challenging tasks in drug discovery...as well as trying to distinguish science facts from science fiction using the power of computers...something I'll post a text on now and then...usually after having read an interesting book/paper.

“This Is Not a Molecular Visualizer”

Cool TechnologyPosted by Jonas Boström Wed, November 18, 2015 23:46:35

Shortly after the first iPhone was launched Olli-Pekka Kallasvuo, the former CEO of Nokia, commented on Apple's new product. The iPhone was brushed off as a niche product, with comments like “this is not a mobile phone”. Kallasvuo was right, it is more than that. Nokia’s mobile phone business has since collapsed. Many others have also failed to recognize the impact of new technology, and have failed to remain innovative and stay on the market. For example, Blockbuster was outperformed by Netflix who made on-demand streaming tv and video available to viewers. Kodak is another giant to falter in the face of advancing technology. Everyone knows that the new king of digital photography is Instagram.

The digital technology is currently changing our world in unprecedented ways. I have previously argued that the time has come for cloud computing. Another exciting example is the recent advances in interaction design creating new and very cool ways to use computer programs. For example, the ability to create highly visual 3D environments that simulates physical presence in the real world – a virtual reality.

Virtual reality was hype in the late eighties, but it never took off. Now, virtual reality is back with a vengeance; affordable with significantly improved performance. Thus, the long-promised technology is becoming mainstream. Virtual reality has begun to play a role in gaming and films. For example, Mythbusters is already shooting in virtual reality. As a moment of affirmation the Time magazine put virtual reality and the Oculus founder Lucky Palmer on the cover of its August issue.

Moreover, Zuckerberg and Facebook acquired the virtual reality startup Oculus with the wordsSo if you go back ten years, most of how people communicated were through text. We’re going through a period where now it’s mostly visual and photos. We’re entering into a period where that’s increasingly going to be video [...] I think immersive 3D content is the obvious next thing after video.

We wanted to give virtual reality a try and developed a tool for molecular modeling (Molecular Rift) as part of a collaboration with the Department of Interaction Design (LTH). The ability to interact with molecular models is relevant to drug discovery since computer-generated molecular models are frequently used to obtain deeper understandings in many areas (e.g. ligand-protein complexes). In fact, visualizing and interacting with molecular models are a significant part of a drug designer’s day job nowadays. The virtual reality environment was created by a talented student using Oculus Rift (a head-mounted display) coupled with the MS Kinect gaming sensor to handle gesture recognition, eliminating the need for standard input devices (keyboard and mouse), providing the drug designer with a more natural way to navigate in 3D.

Student Magnus Norrby, a 10x programmer, demoing ‘his’ Molecular Rift at an internal science symposium

The BIG (and somewhat boring) question – is this very cool virtual reality environment more useful than using traditional molecular visualizers? Well, it should be noted that a virtual reality experience is different from using conventional 3D computer graphics. In the virtual reality, objects have a location in 3D-space relative to the user’s position. Thus the main difference is that you are working with things as opposed to working with images of things. The brain interprets it as you interact with the objects, and you feel like you are really there. The presence changes everything. Traditional visualizers ‘just’ show molecules in front of you, with Oculus a drug designer can enter a protein-ligand complex and look around.

Is that more useful? No one method will ever single-handedly make all the difference in drug discovery (not even CRISPR). Each method, however valuable it is, is one part of the puzzle. That said, if you believe that understanding the 3D component is important, then we believe virtual reality the best way to do it. What we learned during development was that once people try it, they get it. “This is so cool” – was an often heard comment. To compare with sophisticated CAVEs (which are also very cool!), Molecular Rift is easily accessible and the cost for setting up the environment (i.e. Oculus Rift and MS Kinect) is reasonable (a couple of hundred USD). It can easily be used at home or in office spaces. Molecular Rift and its source code have been made open source and is available at GitHub free of charge. We integrated an open-source cheminformatics toolkit paving the way for future development – hopefully in a collaborative and concerted fashion.

Whether Molecular Rift will be the new iPhone of molecular visualizers or be reduced to some kind of exhibition, something to show-off for “important” visitors remains to be seen. If you are interested in the details, the manuscript is here. It includes initial attempts on voice control, and one section with reflections on virtual reality's capabilities in Chemistry and future possibilities. For example, Chemistry as a University subject is certainly not trending. In many countries gloomy pictures are reported. Gamifying learning using Molecular Rift might be one way to motivate and inspire students.

Molecular Rift Is Not a Molecular Visualizer.



Searching for E.T. in Space and Drugs in the Cloud

Cool TechnologyPosted by Jonas Boström Wed, November 18, 2015 23:06:02
This was first posted: 06/04/2013 here

A long time ago, in the state of Denmark, something unusual was going on. All the screensavers in the lab had been changed to new ones. The new ones all appeared to be identical, and they had the same purpose – to search for extraterrestrial intelligence in outer space.

I quickly learned that my Ph.D. supervisor wanted to be part of the SETI@home project. SETI@home was (and is) using screensaver technology to analyze radio signals from outer space. It is now a well-known example of distributed computing. The power of distributed computing quickly becomes apparent when analyzing stats from SETI's first three years – the project accomplished in that time what a single computer would have taken 400,000 years to do.

Within the drug discovery community, Professor Graham Richards at the University of Oxford was an early adopter. Richards and his ”Screensaver Lifesaver” project exploited idle time on 3 million PC’s, cross the globe, to dock 3.5 billion compounds in protein targets. The results from the effort still remain inconclusive however. Among other initiatives, related to drug discovery, Folding@home is probably the most well-known.

Big Pharma are late into the game. Security concerns, both real and imaginary, are/were believed to outweigh possible benefits. This reasoning may be excused since the vast amounts of proprietary data within a company are key assets. Nevertheless, times are changing. Distributed computing within Big Pharma is here – in the shape of a Cloud!


Cloud computing is a synonym for distributed computing over a network and means the ability to run a program (e.g. to search for drugs and aliens) on many connected computers at the same time. The computing resources are typically off-site, available on demand, scalable, and paid per use.

I attended an excellent meeting a few weeks ago. Joe Corkery, VP at OpenEye, gave a very interesting and balanced overview on the current state of Cloud computing in Pharma. It turns out that several Big Pharma’s recently have started to exploit the Cloud; from Virtual Screens to Electronic Lab Notebooks. But the Cloud still generates most traction amongst CROs and small biotechs, where a remotely managed and maintained IT system is seen as of greater economic benefit.

Joe Corkery left stage with a parting thought: “In a pay-per-use world, speed matters.” This observation is often over-looked; the Cloud can be extremely cost-effective when time is a priority. As an example, Joe highlighted that BMS used Amazon's services to build a research Cloud for running computationally intense PK simulations for their clinical studies. In this fashion they were able to reduce the number of enrolled pediatric subjects from 60 to 40. That’s a significant saving!

Moreover, there is now a real incentive to make software faster since one pays for the time one spends in the Cloud. An incentive for getting happy customers that is. On many occasions we, the customers, do not really ‘need’ faster software. But faster software will be cheaper-to-use software. On that note, in the area of computer-aided molecular design it is not uncommon that algorithms and software have been written by non computer scientists. These are typically people who give accuracy more attention than speed and efficiency, instead of all three. So there might be some room for efficiency improvement here…and it’s always possible to make things more efficient, right? As a consequence, speedier software may lead to new ways of using it and lead to unexpected findings. That said, I am personally not in favor of a (pay-per-use) world where there's an obvious disincentive to use the software. This presents a hindrance, small though it may be (a few bucks), that might put people off from launching that extra little investigation…that in the end would have made all the difference.

I believe the Cloud computing is going to be a game-changer. My hope is that large-scale computations will provide a springboard for new scientific achievements. That is, providing opportunities for doing things that were completely intractable before (full flexible docking using quantum chemistry, including explicit waters?!), instead of just doing a lot more of the same in the spirit of “let's switch off the brain and turn on the computers in the Cloud”.

I bet that we’ll find drugs in the Cloud before we find aliens in space. Is there anyone out there, on Earth, willing to take the bet?