automating drug design nov 13th 2009 97

Automating Drug Design

David Leahy

Competitive WorkflowQSAR Example

QSAR Agent

Calculate Descriptors

Model Build

Filter Features

Filter featurerequest ...

Model buildrequest ...

Calculate descriptorsrequest ...

responses

responses

responses

QSAR Agent

Calculate Descriptors

Model Build

Filter Features

Filter featurerequest ...

Model buildrequest ...

Calculate descriptorsrequest ...

responses

responses

responses

CalculateDescriptors

responses

responses

responses

Open QSAR

Wombat Database (thanks to Tudor Oprea)

First 80 data sets (human, n >75, Range > 2 Logs)

Miscellaneous (HSA, Herg, CHI, ClI)

Descriptors

CDK, CDL, MOPAC, HQSAR, E-State, H-State, LSER, AlogP, XlogP

Filter Feature

Hall method

Model Building (Continuous)

RNN, Rlinear, Rpart, RPLS, GUIDE

QSAR Agent

Bus Controller

UserInfo Agent

Datarepository

Info Agent

Modelrepository

Compute Agent

Compute Agent

Service Repository

Meta QSAR Agent

Open QSARhttp://www.openqsar.com/

Community resource for QSAR modelling

Aggregated structure-property data

Model repository

User data and agents

Meta QSAR analysis

Multi-property prediction

Open QSAR. Work in Progress

MOAQ Study

WOMBAT and ChEMBL databases

Classification Model Analysis

Temporal QSAR

Domain of applicability and local models

Open QSAR

Data submission and prediction

New QSAR agents as Inkspot workflows

AmazonBus

Server

AmazonWorkerServers

Security

Virtual Teams

Inkspot Science

Sci Software Services

Workflow

Cloud

MS AzureWorkerServers

Inkspot Science Agents

Inkspot Install to Azure

QSAR Agent

Bus Controller

Datarepository

Compute Agent

Compute Agent

Inkspot Service Repository

Info AgentInfo Agent

Meta QSAR Agent

EC2 Azure

Multi-Objective Optimisation

Agent

Objective Space

Feature Space

Structure Space

QSAR Model

ForagerParticle Swarm Optimiser

ProjectRTP

Scale

Optimise

Search

Get Model

new leads

Colonist Reduced Graph Genetic Algorithm

ProjectRTP

Scale

Optimise

StructureSearch

Get Model

Colonist

Feature SpaceSolutions

Founder population

Build QSAR

StructurePropertyDatabase

Optimised Leads

QSAR Agent

Bus Controller

Info Agent

Datarepository

Info AgentCompute Agent

Compute Agent

Inkspot Service Repository

EC2 Azure

Meta QSAR Agent

MOO Agent DockingAgent

HTS Analysis Agent

Virtual Screening

Agent

Compute Agent

Compute Agent

“The Discovery Bus is not a tool for users. It is a system for doing drug design independent of any user”

The ambition is a step-change in productivity arising from breaking the link between human effort and drug discovery output.