Target Informatics Platform™ (TIP™)

Category Proteomics>Protein Structure/Modeling Systems/Tools

Abstract Target Informatics Platform™ (TIP™) is a novel structural informatics approach for amplifying the rapidly expanding body of experimental protein structure information to enhance the discovery and optimization of small molecule protein modulators on a genomic scale.

In TIP, existing experimental structure information is augmented using a homology modeling approach, and binding sites across multiple target families are compared using a clique detection algorithm.

TIP is one of the world’s first structural informatics system and knowledge base (KB) that enables researchers with the ability to interrogate the druggable genome from a structural perspective.

TIP amplifies the rapidly expanding body of experimental protein structure information and transforms structure-based drug discovery from a low-throughput, data scarce discipline into a high-throughput, data rich science.

Designed to help bridge the knowledge gap between bioinformatics and cheminformatics, TIP supplies drug discovery researchers with a knowledge base of information that is both distinct from and highly complementary to information furnished by existing bio- and cheminformatics platforms.

TIP’s seamless integration of structural data management technology with unique target-to-lead calculation and analysis capabilities enhances all stages of the discovery pipeline.

The TIP Database --

The Target Informatics Platform’s content includes more than 190,000 high resolution protein structures with reliably annotated small molecule binding sites, including >266,000 chains and comparative models of human proteins, covering every major drug target family including proteases, kinases, phosphatases, phosphodiesterases, nuclear receptors, and G Protein-Coupled Receptors (GPCRs).

In addition to TIP’s high quality structural annotation, it is one of the first databases of its kind that stores all similarity relationships between every sequence, structure, and binding site, making it an incredibly advanced system for structural and comparative proteomics.

Most importantly, the TIP database automatically and self-consistently updates itself and computes all relevant similarity information when new protein sequences and structures are uploaded into the system.

This allows customers who deploy TIP behind their company firewall to upload all of their proprietary sequence and structure data into the system, thereby amplifying the knowledge and maximizing the value that can be derived from their proprietary data.

Note: As an alternative to on-site deployment, secure web-based access to the TIP database can be granted through technology license agreements.

TIP Structural Annotation of Druggable Targets --

The TIP database contains a wealth of information about the set of human proteins which have been shown to bind lead-like compounds, commonly referred to as the druggable genome.

TIP Calculation Engine --

Eidogen’s calculation engine for structure determination, binding site annotation, and similarity assessment have been used to generate one of the largest, most highly integrated database of structural chemogenomics information ever created.

Some of the major features of TIP and the corresponding algorithms and software tools responsible for these features are:

1) STRUCTFAST™ - Automated Comparative Modeling;

2) StructSorter™ - N-by-N Structural Alignments;

3) SiteSeeker™ - Binding Site Annotation;

4) SiteSorter™ - N-by-N Binding Site Similarity Assessment;

5) SLiC™ - Site-Ligand Contact Analysis and Binding Mode Similarity Assessment; and

6) LigandCross™ - Knowledge-based ligand generation via binding fragment recombination.

TIP™ Web Portal --

The TIP Web Portal is the backend interface with the TIP™ database, providing a user-friendly, secure, web-based interface for performing advanced querying and data extraction from the database.

With the TIP Web Portal, users are enabled with sophisticated search and sorting tools which allow quick and easy retrieval of relevant structural and binding site information.

Once a set of interesting targets is collected, the user exports a TIP Project file to their Windows or Linux desktop for analysis with the client-side tool, the Eidogen Visualization Environment™ (EVE™) - (see below...).

Key features of the TIP™ Web Portal include:

1) Structure Based Similarity Searching;

2) Binding-Site Based Similarity Searching;

3) Site-Ligand Interaction Fingerprint Similarity Searching;

4) Multiple Limiting Filters to Extract only the Most Relevant Data;

5) Sequence and Structure Upload Capabilities;

6) Automated as well as Manual Binding Site Definitions; and

7) Automated STRUCTFAST Model-Building on Demand.

Eidogen Visualization Environment (EVE) --

The EVE analysis tool allows users to visualize and compare the small molecule binding sites of targets of interest in a matter of seconds.

With EVE’s advanced yet easy-to-use Java3D™-driven interface, both expert and non-expert users alike can quickly analyze and compare important binding site properties and ligand interactions, dramatically enhancing the efficiency with which structure-based selectivity, binding mode analysis, and lead optimization studies can be carried out.

Key features of the Eidogen Visualization Environment™ include:

1) Easy visualization of Sequence, Structure, Site, and Site-Ligand Interaction similarity relationships;

2) Site-Ligand Contact (SLiC) analysis for comparison of ligand binding modes -

3) LigandCross for creation of novel ligand scaffolds from structural data -

4) Easily clone ligands into multiple binding sites to understand the basis for selectivity and cross-reactivity;

5) Perform side-by-side comparisons and overlays of whole protein structures or individual binding sites using pre-computed alignments;

6) Easy mapping and annotation of important binding site properties such as hydrophobicity, charge, hydrogen-bonding capability and pocket depth;

7) Locus annotation for quick identification of targets of interest;

8) Visualization of entire Project Files rather than individual structures enables easy sharing of project data between scientists; and

9) Complete macro language and batch-mode compatibility for carrying out customized, large-scale analyses.

System Requirements

Contact manufacturer.


Manufacturer Web Site Target Informatics Platform (TIP)

Price Contact manufacturer.

G6G Abstract Number 20725

G6G Manufacturer Number 104295