JALEEL

From philosophy to real time experience

Toward a New, Open Source Pharmaceutical IndustryRockefeller Foundation Bellagio Center, July 2014

#opensourcepharma

Literature

Annotation Tools

Genomic Databases

Curated Annotations

Raw Annotations

OSDD C2DCommunity

800+ Student Researchers

Collaborative Curation

Pathway/Interactome | Gene Ontology | Protein Structure/Fold | Glycomics| Immunome

The “Connect to Decode” Programme

Cheminformatics OSDD experience

Curated molecule datasets

Cheminformatics Models

Data Mining and Analysis

HT Virtual screening

PubChem

ChEMBL

DrugBank

Experimental Assays

Community of About 400

Other Active Communities:• OSDD Women Scientists Forum• OSDD Junior Scientists Forum

Pubchem Bioassay data

(approx. 1 lakh molecules/

dataset

6000 descriptors/molecule

Successful Models

Screen PubChem

(30 million)

Data amplification in Drug discovery

Potential Hits

o Down sizing and random validation require multiple calculation for validation of resultso Cross validation up to 50+ time for each experiment

Current Challenges

Around 150 fellows - Open in blogs

TCOF1.3

Workflow

Workflow

TCOWF

April 9, 2023 CSIR-OSDD Research Unit, Indian Institute of Science, Bengaluru

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THE WORK PLAN

April 9, 2023 CSIR-OSDD Research Unit, Indian Institute of Science, Bengaluru

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MATERIALSSELECTION OF BIOASSAY

• Bioassay AID 434987 for Model.• Inconclusive Datasets.

PATTERN

SEARCH

• Descriptors by Power MV.• Random Forest Model by WEKA.

PROMSCUITY

• Non- specific Interactions.• 275 rules to conclude if a compound is promiscuous by Eli-Lilly.

NEURAL NETWORKS

• an unsupervised training.• SOM; Kohonen network is used.

LIGAND-

TARGET

INTERACTIONS

• Glide- Schrodinger.• Prioritization of the molecule.

April 9, 2023 CSIR-OSDD Research Unit, Indian Institute of Science, Bengaluru

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April 9, 2023 CSIR-OSDD Research Unit, Indian Institute of Science, Bengaluru

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SCREENED RESULT IN JCHEM EXCELChemAxon (AID 895)

April 9, 2023 CSIR-OSDD Research Unit, Indian Institute of Science, Bengaluru

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LILLY MEDCHEM RULES CLASSIFIED MOLECULES

PubChem Dataset

AID

Number of

Inconclusive

Molecules

Lilly MedChem rules

classified molecules

895 795 75

906 30 03

928 870 80

942 18 01

1533 1058 111

1626 3501 262

1949 3175 366

434955 4331 414

• Reasons for rejection include reactivity, interference with assay measurements, activities that damage proteins, instability, and lack of druggability.

• The molecules which are found to be good are separated and saved as an SDF file in each case.

April 9, 2023 CSIR-OSDD Research Unit, Indian Institute of Science, Bengaluru

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HIERARCHICAL CLUSTERING

• Of aid 434987 actives and predicted actives from inconclusive datasets.

April 9, 2023 CSIR-OSDD Research Unit, Indian Institute of Science, Bengaluru

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SELF ORGAINIZING MAPS

• SOM uses neural network to perform virtual screening for compilation of thematic molecular libraries.

• Unsupervised training.

• A particular kind of SOM known as Kohonen network is used.

Aminobenzimidazole series

NH

NNH

OSO O

NH

NNH

OSO

NH

NN

OSO O

NH

NNH

OS

OO

NH

NH

OSO O

NH

N HN

SO O

O

NH

NNH

OSNH2

O O

NH

NNH

OHN

S

O

O

N

NNH

OSO O

O

NNH

OSO O

S

NNH

OSO O

N NH

NNH

OSO O

Thiazolylurea series

S

N

NH N

H

S

S

N

NH N

H

O

O

N

NH N

H

S

NH

N

NH N

H

S

S

NN

NH N

H

S

NH

NN

NH N

H

S

S

N

NH N

H

S

S

N

NH

S

S

N

NH

S

S

N

NH N

H

SHN

S

N

NH N

H

S

S

N

NH

SHN

Benzoylpyrrolidone series

O

N O

O

O

N O

O

O

N

NH

O

O

O

N

O

O

O

N O

O

O

N O

O

N O

Cl

O

N O

S

O

N O

S

O

O

N O

HN

O

N O

H2N

O

O

N

N

O

OO

NN O

O

O

NHN O

O

TCOF.1.1

Random forest in CUDA • User Manual or Documentation

http://ajaykmathias.files.wordpress.com/2014/07/virtualscreening.pdf

Installation Manualhttp://ajaykmathias.files.wordpress.com/2014/07/installation-manual.pdf

• Checklist for Virtual Modelling and Screening Processhttp://ajaykmathias.files.wordpress.com/2014/07/screen.xlsx

Mutagenicity studies

Various stages Various models

Open lab

Social networks

OSDD OPEN LAB

OSDD Research Communities

TATA FELOWSHIPS