Arbor Vita created the PDZ Drug Discovery Platform to characterize interactions between PDZ proteins and PDZ ligands (PLs). The Platform is a focused and rational approach to drug discovery which utilizes a combination of public and proprietary bioinformatics tools; in silico molecular modeling and virtual screening tools; a library of properly folded PDZ proteins; laboratory information management; and the Company's high-throughput screening assay. In preliminary screening, Arbor Vita has discovered over 1,200 novel interactions—each one a potential drug target.
Definitive PDZ Protein Reference Set
Arbor Vita has reduced the target discovery and validation process from months to days by creating a comprehensive, properly folded PDZ reference set. The reference set permits high-throughput screening for small molecule drugs that will target any PDZ/PL interaction with specificity. The Company has leveraged existing technology in a focused and rational approach to create the AVC Database: a PDZ/PL reference set for drug discovery. Using information from the Human Genome Project, Arbor Vita has cloned and expressed nearly all the known human PDZ protein domains (approximately 330) into properly folded recombinant proteins to create a PDZ reference set. Arbor Vita has also created a comprehensive set of PLs and tested pairwise combinations to create a reference set of PDZ/PL interactions. The proprietary AVC Database contains all of the Company's experimental data including the PDZ and PDZ/pL reference sets.
Bioinformatics and In Silico Molecular Modeling
Arbor Vita has created a proprietary predictive bioinformatics tool that includes computer-based (in silico) molecular modeling that allows scientists to quickly assess the potential biochemical significance of each molecular interaction. Utilizing x-ray crystal structure information on PDZ proteins, the Company has developed an accurate and testable set of computer models for PDZ domains. Using the experimental data in the AVC Database, models of PDZ/PL complexes are used to direct small-molecule screens. Analysis of the data from such screens will allow Arbor Vita to further refine the docking models to reflect small-molecule binding. Validation of the in silico results can then be accomplished utilizing the Company's AVC Matrix assay. To maximize value, the system is integrated with public and proprietary discovery research tools, relevant articles from the scientific literature, and other protein and nucleic acid databases.
The AVC Matrix HTS
The AVC Matrix is a high throughput screen (HTS) that uses properly folded human proteins to ensure that interactions identified via the AVC Matrix HTS are true and relevant to actual biological systems. The AVC Matrix HTS is rapidly scalable to meet high-throughput therapeutic compound screening needs. The proprietary AVC Matrix HTS quickly and accurately identifies novel interactions, titrates interactions to assess actual binding affinities, and assesses the efficacy of potential lead compounds at blocking interactions. The AVC Matrix HTS can be inexpensively automated with robotics, thus the capacity for expansion is virtually unlimited.