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So You’re Going
The Environment is changing Top 10 causes of death*
1. Heart disease
*WHO fact sheet 2015 globally (http://www.who.int/mediacentre/factsheets/fs310)
2. Stroke
3. Lower Respiratory infections
4. Chronic Pulmonary diseases
5. Cancer (trachea, bronchus)
6. Diabetes
7. Alzheimer disease
8. Diarrheal diseases
9. Tuberculosis
10. Road injury
Deaths in millions
Only one cause not related to disease
Virtual Reality in Drug Design
Jonas Boström, AstraZeneca, Medicinal Chemistry, CVMD
May 16th 2017, VR World, London, UK
VR for Drug Designers
Molecular Rift creates a VR environment using Oculus Rift goggles. Users can interact with molecules through gestures
Computer-aided Drug Design is about designing and making compounds with desired properties using computers, with the grand mission of designing new drugs for treatment of diseases
Using data to find patterns
3D-Shape and electrostatics
Generate knowledge for faster and better decisions Secure high information content for every compound made
Akin to Weather Forecasting D
Err
or
in T
em
p (
F)
Year 2010 2000 1990 1980
6.0
3
.0
4.0
5
.0
Errors in predictions goes down with time
2005
2015
Computing Resources
Humans Still Needed
“If you can describe it, we can program it”
Drug Design: A Multi-Parameter Problem
Chemical synthesis
Potency Solubility
Permeability
Metabolism Patentability
Stability
Distribution
Toxicology
Team
Inhibit or Activate Some Target Protein
Approach depends on whether the 3D structure of the protein is known or not
Known – ”Structure-Based”
Not known – ”Ligand-Based”
OO
OH
NH
Seloken ®
OO
OH
NH
Linker
”Lock and Key”
What we can make…
1063 molecules: R.S Bohacek et al. Med Res Rev 16 (1996) pp. 3–50. 1024 molecules: P. Ertl JCICS 43 (2003) 374-380.
Synthesizing 1024 molecules would take 1 000 000 000 000 000 000 years provided… 1000 chemists makes 1000 compounds each per year
…given enough time
Can predict nothing Buy more tickets * Driven by synthesis
Can predict something Place bets based on previous form * Driven by design
We must choose what to make
Chemical space is huge. Use data, algorithms and IT: faster, cheaper and better
Molecules are 3D objects All molecules ranging from structurally simple drugs like aspirin to complex systems like
proteins to the famous DNA double helix are 3D objects
.…visualizing and interacting with molecular models is part of a drug designers day job
Knowledge about their 3D structure is important in most stages of drug discovery
One Simple SBDD Example
pdb: 1ftm (GLUTAMATE RECEPTOR SUBUNIT 2) SBDD Review: Anderson, A. C., The Process of Structure-Based Drug Design. Chemistry & Biology 2003, 10, 787-797
Identify empty space in binding pocket
One Simple SBDD Example
pdb: 1m5b (GLUTAMATE RECEPTOR SUBUNIT 2) SBDD Review: Anderson, A. C., The Process of Structure-Based Drug Design. Chemistry & Biology 2003, 10, 787-797
Fill empty space in binding pocket
3D Molecular Viewing Tools With the rise of efficient computers, the focus switched from physical representations to
computer generated models.
Stand-alone Rasmol, PyMol, VIDA and now web-based systems Jmol, AstexViewer, iView. an important innovation here was the ability to display stereoscopic 3D views.
Virtual reality for Drug Designers But even with the stereo, traditional visualizers ‘just’ show molecules in front of you; with VR a drug designer can enter a protein-ligand complex.
Surprisingly few examples of VR in drug design
Molecular Rift
Molecular Rift creates a VR environment using Oculus Rift goggles. Users can interact with molecules through gestures
The first easily accessible Virtual Reality tool for Drug Design
Details Oculus Rift goggles are used to create to the VR environment. Gesture recognition (interaction) MS Kinect (v1) Leap Motion (v2), Development: Unity game engine (MS Kinect v2) Leap Motion SDK Oculus Runtime OpenBabel – open source cheminformatics tool-kit. Programming: Windows and mainly C#
Molecular Rift v1 MS Kinect (X-box)
Molecular Rift v2 Leap Motion and controller
Oculus Rift
Gesture-Based Interactions Traditional input devices (mouse and keyboards) are not ideal with goggles
Graphical Representations Built from scratch, using the game-engine Unity
Objects (atom, bonds, etc) are rendered from coordinates parsing pdb, sdf, mol2 Small molecule representations: lines, ball-and-stick, stick, CPK
Creating protein/DNA ribbons
Intermolecular H-bonds
Residues can be labeled
Pharmacophore objects
Coloring schemes
Features
In-game menu
24 (keyboard shortcuts implemented)
More Useful?
communication
Compare with the technology evolution to that which occurred for normal phone calls:
Before we called, we now use FaceTime/Skype to see that we are talking to.
In essence, it is almost the same, but a new and improved experience.
“Although cool, is Molecular Rift more useful than traditional molecular visualizers”?
What’s the difference?
3D viz
In essence, it is almost the same, but a new and improved experience – it’s more efficient ….and drug design is not all that rational, there’s a portion of creativity
and VR comes with an inherent “wow this is cool!”
Focus groups
red is good [here]
If only people tried before asking
Prominent testers have experienced atoms and molecules using our virtual reality tool.
H.M. King Carl XVI Gustaf The Sports Minister of Chile The Executive Vice President at AstraZeneca (a gamer) The Head of Business Development at EA Sports … …
You’ve got 3 minutes…
representing AstraZeneca at Investor's 100th anniversary event
Demonstrating how to use Virtual Reality (VR) in the development of drug molecules
and What Science Can Do!
Investor is AstraZeneca’s second largest shareholder with a holding of approx. 4% of total shares
Taking me places (London)
People and papers
Magnus Norrby, Master Student Jonatan Enström, Student Christoph Grebner, Post-Doc
GitHub – free to one and all Version 1 – MS Kinect https://github.com/Magnusnorrby/MolecularRift Version 2 – Leap motion https://github.com/JBostrom/MolecularRiftv2/tree/master/DK2 (Development 2 version) https://github.com/JBostrom/MolecularRiftv2/tree/master/CV1 (Consumer version) HTC Vive https://github.com/UoA-eResearch/MolecularVive
Open-source
(ported by guy in New Zealand!)
Molecular Rift used @AZ?
Nope 1 – not good enough for expert users, yet.
Features lacking
* being able to modify docked molecules.
* not possible to create surfaces
* …
Nope 2 – Other obstacles
* AZ computers are not high-end
* “IT Security exception process must be approved”
* …
VR Predictions Smartphones and Google Cardboard-like tech will conquer VR.
Mobile apps enables VR experiences without having to invest into extensive systems.
Does not need a high-end PC to run applications.
It’s truly mobile (no wires)
Hardware is cheap, if not ‘free’
(most people already have a smartphone).
Performant
Google Daydream, Samsung GearVR
VR is great for many things
training, real estate, phobias, education, …
VR in Chemistry Education* Vision is to engage more students in chemistry using virtual reality.
Giving us more drug designers?
* A former student and I started a separate EdTech VR Company last year
EduChem VR ”Freemium” apps Three freemium virtual reality apps available on Google Play (Android) and AppStore (iPhone)
* try zooming through a carbon nanotube or going on VR DNA roller-coaster
EduChem VR also make tailor-made apps, for a range of VR systems (HTC Vive, GearVR, Daydream, …)
VR Chemistry Education Use-Case
pen & paper/whiteboard/physical models
Virtual Reality experience more efficient and better for learning tool
“StereoChemistry is just one concept which is difficult to explain with paper&pen/white-board. It can take a day to put up such an exercise using traditional methods. With your VR apps this is instant and the technology is applicable in all
our courses.” Ass Prof C-J Wallentin
Launch a VR app, place the smartphone app in the Google Cardboard …and teachers/students are teleported into a virtual world of atoms and bonds
The Future of VR in Drug Design
Augmented Reality Drug Design is team work From single-player mode to multi-player, toward a more collaborative virtual reality There are other VR tool than ours … UnitMol, ChemPreview, Nano-one, …
Get and try our smartphone apps? http://www.educhem-vr.com
Follow me into the Virtual Reality Get and try the smartphone apps?
http://www.educhem-vr.com
Smartphones, apps and virtual reality Vision:
make chemistry the coolest subject to learn using easily accessible virtual reality (VR)
combing chemistry, IT and programming knowledge
EduChem VR founded in Sweden, September 2016 by
Dr. Jonas Boström, CEO Principal Scientist and Associate Professor
Drug designer in Big Pharma since 15yrs
Recognized molecular modeller
50+ articles and patents
Magnus Norrby, CTO Professional programmer in Finance
Main developer of open-source Molecular Rift
Domain knowledge in virtual reality and cheminformatics
have a history of delivering powerful and user-friendly tools to enhance drug discovery. An example is the Oculus Rift based VR molecular
visualizer.
The EduChem VR board includes senior scientists:
a professor in Biology and a professor in Chemistry
