So You’re Going - vrworldevent.com · Leap Motion and controller Oculus Rift Gesture-Based...

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