Aragen-IDD has extensive experience in computational modelling, informatics and data-driven solutions in the field of drug discovery & development. Experienced CADD team members at Aragen-IDD work hand-in-glove with the medicinal chemists towards generation of new ideas for design of novel compounds. These ideas are aimed at improving the physicochemical properties within the series during lead identification & optimization leading to preclinical candidates. The technologies span across the spectrum of computational techniques such as homology modelling, protein structural analysis including identification of cryptic pockets of ligand binding including the basis and design of ligand selectivity. The state-of-the-art facility at Aragen with its advanced computing software enables the team to carry out long and complex molecular dynamic simulations to understand the affinity & stability of protein-ligand complexes. The team has successfully delivered legitimate hits & leads heading to preclinical candidates in various programs comprising of both small molecules and Targeted Protein Degradation (TPD).
Computer Aided Drug Design (CADD)
CADD group at IDD has both the technology and expertise in various classes of drug targets (e.g. Kinases, GPCRs, Ion channels, Nuclear receptors etc.) involving different modalities like orthosteric, allosteric & covalent small molecules binders as well as degraders and molecular glues. The group over the years had sucessfully worked towards information guided solutions in various projects in drug discovery and developemnt. The various verticals fo CADD capabilities are summarised below
- Structure Based Design: Aragen team’s experienced in understanding the structural biology of a given protein target and the science of its modulation. Understanding the structure of the protein and the follow-up analysis of the modulator binding site geometry including its flexibility is the prime importance in any structure-based drug discovery programs. At Aragen we have the capabilities to carry out long term Molecular dynamics simulations to understand the dynamics of the protein active site geometry with respect to its modulator binding. This also includes the free energy calculations for determining the protein-ligand affinity. In the absence of any structure – either X-ray or CryoEM – the CADD group has the experience of building homology models of complex multimeric structure for proteins like Ion channels and similar druggable proteins of interest. Additionally we have a unique and proprietary virtual library of compounds with druggable characteristics (adhering to RO3 & RO5) for virtual screening on any given protein target of interest.
- Ligand Based Design: Ligand Based Design has also been an integral part in Aragen’s Drug Discovery projects. We have been successfully using the ligand based design approach to obtain leads in many complex targets such as RNA modulators etc. We have the capability to work on shape-based screening that relies on the Pharmacophoric features and the 3D geometry of the molecules. Tools and techniques are in place to carryout scaffold hopping and R-group modification studies as well. Towards this end, proprietary databases of unique fragments for the identification of drug-like molecules for lead optimization leading to clinical candidates have been generated. These fragments are of different properties catering to different therapeutic areas such as oncology, CNS and anti-infectives.
- Targeted Protein Degradation Design (TPD) ML based Toolbox: Designing targeted protein degraders using computational techniques has been a major strength at Aragen IDD. We have developed a virtual database of linkers, E3 ligase binders and their combination. These linkers and E3 ligases are also enabled at Aragen. With the experience of designing TPDs in various drug discovery programs with partners and also the information available in the public domain, the CADD group has developed an in-depth understanding of modelling TPDs and developed a proprietary workflow for the same.
- AI/ML toolbox for Lead generation: IDD Aragen has developed tollbox of fingerprints for property-directed lead generation leveraging the information available in public domain. These fingerprints are used for developing ML-based predictive tools for guiding the property generated molecules for therapeutic specific areas.
Integrated Digital Workplace:
- Design-Make-Test-Analyze cycle :
IDD has developed a digital platform for ‘Design-Make-Test-Analyze’ (DMTA) cycle and compound data management system (CDMS) in the Discovery process. This platform is an integration of there digital tool as well as customised automated platform for data acquisition, data transfer and data analysis. It is the integrated discovery workflow for CADD-Medchem-Biology-DMPK that ensures easy tracking, smooth data transfer and clear visualization across the various project stake holders.CDMS is designed to have an integrated digital process platform from compound registration to assay results and data storage for analysis. IDD’s partners can directly monitor the projects in real time and make compound assay requests directly from partner’s location.
Aragen’s in-house Knowledge base:
Leverage the extensive experience in the field of informatics driven drug discovery solutions, the team had developed its own proprietary fingerprint-based knowledgebases and algorithm guided technology platforms to aid various projects.
These proprietary knowledgebases are unique and advantageous toward building of value creation in IP using the internal fingerprints leveraging our proprietary platform technology.
