Andrey Voronkov* and John Shultz *av@drugdiscoveryathome

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Drugdiscovery@home - distributed volunteer computing project in the fields of cancer, aging and stem cells Andrey Voronkov* and John Shultz *[email protected]

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Drugdiscovery@home - distributed volunteer computing project in the fields of cancer, aging and stem cells. Andrey Voronkov* and John Shultz *[email protected]. Computational tasks go from server to locally or globally distributed computers and computed results go back to the server. - PowerPoint PPT Presentation

Transcript of Andrey Voronkov* and John Shultz *av@drugdiscoveryathome

Page 1: Andrey Voronkov* and John Shultz *av@drugdiscoveryathome

Drugdiscovery@home - distributed volunteer computing project in the fields of cancer, aging

and stem cells

Andrey Voronkov* and John Shultz

*[email protected]

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What is VCSC and distributed computing?Computational tasks go from server to locally or globally

distributed computers and computed results go back to the server.

Internet – volunteer computing

ProjectsVolunteers

Helps science

Involves public in sciencehttp://boinc.berkeley.edu/trac/wiki/BoincPapers

Local network – VCSC

BOINC server

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DRUGDISCOVERY@HOME PROJECT WORKFOW

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METHODS OF THE PROJECT:• Distributed computing, GPU computing• Virtual screening with flexible amino acids• Relaxed complex scheme for docking• Molecular dynamics with explicit solvent models for protein-

ligands complexes stability evaluation• Pathway interactive mapping with dynamics changes modeling

FIELDS OF THE RESEARCH:• Biotargets involved in stem cell niches signaling pathways• which are related but not limited to cancer and

neurodegenerative diseases pathways. Biotargets which fit to cancer/aging regulation according to hypothesis on Pic. A.

• Example of biotargets: proteins involved in Wnt, Shh and Notch signaling pathways.

• Other biological targets, related to cancer, degenerative diseases and stem cells biology can be considered in collaboration with the experimental biologists groups.

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The working hypothesis of cance/degeneration and symmetric/asymmetric division of stem cells

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ACCOMPLISHMENTS:– Initial integration project website with Drupal– High throughput Molecular Docking CPU 

• Distributes Python• Distributes some MGLTools Packages• Managed by BOINC Wrapper

– GROMACS integration with BOINC Wrapper for CPU• Simulate 100 ps in 2.5 hrs• Trajectory Files Range from 10-40MB • Results compress with 7zip format

– Autodock 4.0 integration with BOINC Wrapper for CPU– Protein-ligand docking->MD workflow setup (acpypi)– Major Platform Integrations

• Windows• Mac PPC & Intel• Linux

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Team:• Andrey Voronkov, PhD, Moscow State

University, department of chemistry – project leader, molecular modeling, drug design, BOINC server setup

• John Shultz, National academy of sciences, Washington D.C., IT, coding, BOINC server setup

• Jorden van der Elst, main software tester• Also we collaborate with several people from

industry, which make systems biology part and which want to be undisclosed for now.

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COLLABORATION

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OPTION 1: Collaboration with the experimental biologists

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OPTION 2: Virtual Campus Super Computing for universities and organizations

Advantages against cluster supercomputing:• New pool of computing power for very low cost• Enhanced stability compared to clusters & supercomputers• Applications not built for the cluster architecture• Positive PR for University

 Advantages against distributed volunteer computing:• Purely VCSC, no volunteers outside network

o No Credits, no cheaters, only need one result per workunit (better performance per 1 CPU), better security, more flexible regarding software licenses

• Volunteer Projecto Need to preven cheating, validate results, more limitations on

redistributing licensed software 

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Examples of applications for drug design

1 average CPU Molecular dynamics of 100 aminoacids of complex of protein with small molecule ligand with explicit water and explicit salts during 2 days

100 picoseconds

VCSC

with 200 CPUs

100 trajectories by 100 ps for one complex or

100 different ligand protein-complexes by one 100 ps trajectory

VCSC increases computing resources by several orders of magnitude and enables to apply some of the existing software application to more of objects.

Example 1. Virtual screening by docking of organic compounds to biotargets.

Example 2. Molecular dynamics of protein-ligand complexes with explicit water molecule models

1 average CPU ~1 000 000 compounds screened by rigid protein model docking with Autodock 4.0

100 days

VCSC

with 200 CPUs

~ 1 000 000 compounds Autodock 4.0. docking to rigid protein model or ~ 50 000 compounds docking with flexible protein model

1 day

GPU usage can increase computing resources from ~10 to 50 times against CPUs

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I. Campus virtual supercomputing center BOINCserver setup• I.1 Evaluation of potential computing resources and server requirements• I.2 BOINC server setup

II. Communication with computer owners and system administrators

III. Communication with computational scientists• Identification of scientists with computationally-intensive applications that map well to volunteer computing.• Porting of applications to BOINC• Applications compilation for CPU Windows/Linux• Applications compilation for GPU Nvidia/ATI AMD• BOINC options setup (priority system, tasks limits) IV. VCSC maintenance

TOTAL TIME for VCSC: 2-3 human*months

Virtual Campus Supercomputing Center creation process

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PLANS (2 years):1) GPU coding for applications and BOINC client – significant increase of

computational power for virtual screening and molecular dynamics with explicit solvent models.

2) Implications of several protein flexibility methods like relaxed complex scheme and protein Monte Carlo dynamics.

3) Dynamic modeling of signaling pathways network which must result in interactive mapping and prediction of most prospective biotargets for suggested diseases.

4) Drug design and biological compounds trials for prospective biotarters of Wnt signaling pathway (1st year) ~8-10 biotargets, and Shh, Notch and other stem cell niche regulating proteins for the second year (10-15 biotargets).

Funding required 150 000$/year:-full-time salary for 4 persons, hosting, some software licenses

Funding alternatives which are considered now: - Grants for small entities - required to make project as non-commercial (in

collaboration with universities)- Sales and services (volunteers profits sharing, initial general business plan

available upon request), an office required, preferably in Maryland, US

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Thank you for the attention!