Distributed Drug Discovery

Indiana University Purdue University, Indianapolis

Introduction:

PURPOSE

OUTLINE

DESIGN

IMPLEMENTATION

FUTURE WORK

Purpose

Need for innovative and inexpensive drugs to treat diseases in the developing world.

Developed world has the equipment and procedures in the pharmaceutical industry through the economic incentives.

Developing countries do not have the required economic incentives for the pharmaceutical industry.

Concept

Concept of “Distributed Drug Discovery” is that if simple, inexpensive equipment and procedures are developed for each of the core scientific drug discovery disciplines (computational chemistry, synthetic chemistry and biochemical screening), large research problems can be broken down into manageable smaller units and carried out at multiple academic sites throughout the developing and developed world.

The coordinated and recombined results of these resources would inexpensively accelerate the identification of leads in the early stages of the drug discovery process.

Procedure

A list of potential drug lead candidates could be split up into small batches for synthesis in academic laboratories throughout the world.

Then the pooled molecule products can be tested by the distributed screening effort.

The summation of these efforts, networked across the three core disciplines, becomes a powerful globally distributed drug lead process and solution.

Procedure (contd.)

The synthetic laboratory experimental work is done in three main locations around the world including IUPUI.

Enumeration software is used to create large sets of potential product molecules called virtual libraries.

These in turn are rehearsed by students using a distributed approach theoretically.

This distributed project can be made successful with the help of information technology to coordinate the dissemination, recollection and analysis of data.

Outline

To keep track of the data used and produced, a Distributed Drug Discovery Database is generated.

Featureso Entry of reagents in databaseo Generation of combinatorial productso Entry of synthesized products information

Release:o Web application to enable data entry/searching of

D3 databaseo Workflow environment to support pipelining of

tasks involving D3 database o Web services to facilitate integration with other

resources (e.g. PubChem)

Database

Database: PostgreSQL User Interface: Java and HTML Tomcat Server and JDBC driver Chemaxon

o Marvin Sketcho Marvin Viewo JChem Reactor

Entity-Relationship Diagram

Tables

1. Reagents Table2. Virtual Library Table3. Rehearsed Library Table4. Synthesized Library Table5. Source Table6. Organization Table

Web Interface

Created a web interface using Tomcat 5.5, html and JSP.

The front end is in HTML and the back end is in JSP.

Web interface connects to the backend database using Tomcat 5.5.

WORK FLOW FOR INTERFACE

Login Page

Administrator Student

Administrator

Search the database Update the Database

Search the ReagentsSearch the products

Populating the Database

Contd….

Enumeration Using Chemaxon Reactor

Chemaxon’s Marvin Reactor enables the user to enumerate the virtual library.

The Reactor program is embedded in the web application.

first the user selects a reaction for the experiment: from a standard set of reactions draw his/her own reaction in Marvin sketch upload using smarts.

Second the user selects the reagents involved in the reaction

The results are also available in a downloadable format.

Selecting a Reaction

Selecting the Reaction (contd.)

Setting the Reactants

Results

Student WorkBook

integration Student Workbook into the Web application used to populate the synthesized table Moving data from students table to synthesized table

is performed by the administrator Also used to grade students

Contd.

Can be accessed at http://cheminfo.informatics.indiana.edu:8080/ddd/first.html Input based on student name, team number and

organization name.

Contd.

User is given the choice of experimental vessel in which he wishes to input the data as shown below

Contd.

Next the student enters the data of the experimental work. The user can enter incomplete data and then come back to

update the experiment. If the user is not having sufficient data for input, he can input

the available data and return back at a later time to enter the remaining data.

The interface is capable of retrieving the previous information entered with the authentication of Student last name and team number.

Marvin Sketch is embedded to enable users to draw the product structure and copy it as SMILES to enter the data in the database.

Since the data entered could be retrieved, the user can always make changes if he realizes that he has entered incorrect data.

Contd.

Usability Study

A usability study is being conducted on the student interface.

To study the feasibility and usability of the Web application for the students.

Points Considered for Survey• Website design i.e., user-friendly, legibility of

instructions, size of fields, etc.• Use of Marvin Sketch i.e., usefulness, complexity and

overall impression.• Database Entry i.e., paper Vs. computer,

updating/editing information• Rating of the overall web application

Results

Contd.

Contd.

Contd.

Contd.

Students were a bit confused in the beginning to use the web application.

Though the application needs to be polished, the database is very useful in storing the outcomes of the experiments.

Found Marvin Sketch similar to Chemdraw, but were confused why they were using Marvin.

Overall the web application was a good one.

Administrative Interface

Administrator is given a choice of searching the student input by Student Lastname Product Structure Team number Vessel number

Interface of Product Structure Input

Result

Search by Vessel Number

Result

Contd.

Once the administrator checks the experimental results, He can grade the students Check for the correct product structures Omit the ones which are wrong and Input the right ones into the synthesized library Can send these results for further investigation to

laboratories

Future Work

Supporting more popular queries:Extracting the Reagents from Aldrich and storing them in

our database. Test and fine tuning of the distributed application Transform popular queries into web services (e.g.

combinatorial queries into web services)

THANK YOU!