So You re Going
The Top Environment 10 causes of is changing death* 1. Heart disease 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 Only one cause not related to disease Deaths in millions *WHO fact sheet 2015 globally (http://www.who.int/mediacentre/factsheets/fs310)
Virtual Reality in Drug Design Jonas Boström, AstraZeneca, Medicinal Chemistry, CVMD May 16 th 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
D Error in Temp (F) Akin to Weather Forecasting 6.0 2005 3.0 4.0 5.0 2015 1980 1990 2000 2010 Year Errors in predictions goes down with time
Computing Resources
Humans Still Needed If you can describe it, we can program it
Drug Design: A Multi-Parameter Problem Chemical synthesis Potency Solubility Stability Patentability Team Permeability Distributio Metabolism n Toxicology
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 Lock and Key O O Seloken OH N H O Linker O OH N H
What we can make 10 63 molecules: R.S Bohacek et al. Med Res Rev 16 (1996) pp. 3 50. 10 24 molecules: P. Ertl JCICS 43 (2003) 374-380.
given enough time Synthesizing 10 24 molecules would take 1 000 000 000 000 000 000 years provided 1000 chemists makes 1000 compounds each per year
We must choose what to make Can predict nothing Buy more tickets * Driven by synthesis Can predict something Place bets based on previous form * Driven by design 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 Identify empty space in binding pocket pdb: 1ftm (GLUTAMATE RECEPTOR SUBUNIT 2) SBDD Review: Anderson, A. C., The Process of Structure-Based Drug Design. Chemistry & Biology 2003, 10, 787-797
One Simple SBDD Example Fill empty space in binding pocket pdb: 1m5b (GLUTAMATE RECEPTOR SUBUNIT 2) SBDD Review: Anderson, A. C., The Process of Structure-Based Drug Design. Chemistry & Biology 2003, 10, 787-797
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 The first easily accessible Virtual Reality tool for Drug Design Molecular Rift creates a VR environment using Oculus Rift goggles. Users can interact with molecules through gestures
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#
Gesture-Based Interactions Traditional input devices (mouse and keyboards) are not ideal with goggles Oculus Rift Molecular Rift v1 MS Kinect (X-box) Molecular Rift v2 Leap Motion and controller
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? Although cool, is Molecular Rift more useful than traditional molecular visualizers? 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. communication In essence, it is almost the same, but a new and improved experience.
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!
If only people tried before asking Focus groups red is good [here]
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
Taking me places (London) representing AstraZeneca at Investor's 100 th anniversary event Investor is AstraZeneca s second largest shareholder with a holding of approx. 4% of total shares Demonstrating how to use Virtual Reality (VR) in the development of drug molecules and What Science Can Do!
Magnus Norrby, Master Student Jonatan Enström, Student Christoph Grebner, Post-Doc People and papers
Open-source 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 (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 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 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
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