Locus Pharmaceuticals acquires Protein Mechanics

Blue Bell, PA-based Locus Pharmaceuticals has acquired Protein Mechanics, a four-year old US West Coast-based drug discovery company which developed ground-breaking simulation technology for the design of small molecule therapeutics.

This novel and proprietary computational technology evolved from nearly 20 years of cross-disciplinary simulation research of complex, dynamic mechanical systems in the engineering industry.

Protein Mechanics was founded on the principle of applying this in silico engineering approach to the simulation of protein movement, which results in highly accurate protein structures that are critical to the success of de novo drug design. This ground-breaking simulation technology is highly synergistic with Locus' strength - the ability to computationally design novel drug candidates specific to selected clinical protein targets. The union of these technologies will substantially broaden the scope of drug targets, improve the accuracy of the drug design process and decrease the overall cost of drug discovery.

'The Protein Mechanics technology acquisition represents a unique and compelling merging of proprietary know-how which substantially accelerates our business model' said Dr H Joseph Reiser, president and ceo of Locus Pharmaceuticals. 'When fully integrated with our proprietary fragment-based drug design approach, Locus will be in a strong leadership position in the de novo drug design arena.'

Locus's proprietary core technology (LCT) rapidly identifies viable drug binding sites on the surface of proteins and directs the de novo assembly of fragments into small molecule product candidates. As applied to Locus' corporate projects in AIDS, inflammation and cancer, LCT has reliably provided highly active and novel lead molecules which are now advancing toward clinical development. Locus's unique computational approach has demonstrated distinct advantages over more traditional drug discovery methods such as high throughput screening and in silico molecular docking methods.

Computational drug design approaches such as LCT, however, are fundamentally dependent on a protein structure as a starting point. Protein crystallography provides an accurate snapshot of a protein structure in time, but proteins are in constant motion, and this snapshot is only a small window of the full spectrum of structures that exist and could serve as drug targets. Thus, the ability to accurately model protein movement or flexibility is a key determinant in the success of drug discovery. Protein Mechanics technology addresses this current void in the design of new drugs by its ability to manipulate protein structures computationally. Protein Mechanics' software platform, Imagiro, forms the basis of a substantial patent portfolio.

'As an analogy, when you apply Imagiro to a target protein, the software can analyse the protein movement much like a system of interconnected girders and from that predict motion in the same way that an engineer would predict the flexing of a skyscraper during an earthquake' said Dr Jeffrey Wiseman, corporate vice president, technology and informatics at Locus.

Combining the Locus and Protein Mechanics technology should provide the following advantages:

New binding sites: LCT provides rapid and accurate determinations of specific protein binding sites and the generation of novel, small molecule compounds designed precisely for those sites. Applying the Protein Mechanics technology reveals protein motion which uncovers potential new protein surfaces and allows designing of new compounds with desirable therapeutic profiles, often times the difference between success and failure in creating new medicines.

Selectivity and toxicity: The ability to rapidly and accurately compute protein structures across families of closely related proteins allows Locus to computationally address one of the major sources of drug toxicity inherent in cross-reactivity. Locus scientists will be able to anticipate cross-reactivity of new drug compounds with critical proteins that would give rise to harmful effects in therapeutic use - and efficiently design out these liabilities early in the drug discovery process.

Homology modeling: As Locus scientists calibrate and refine the accuracy of our protein structure computations, we will be able to target therapeutically critical proteins that currently cannot be crystallised, such as membrane-bound proteins. Homology modeling will extend Locus's structure drug design capabilities to the full spectrum of the human and pathogen genomes.

About Locus

Locus is already a leader in the successful application of a computational-based drug discovery approach that provides novel therapies for important diseases such as AIDS, Cancer and rheumatoid arthritis. It is a privately held pharmaceutical company focused on developing novel, small molecule therapeutics to address major unmet medical needs. Locus combines powerful and proprietary, fragment-based, computational technology with one of the world's fastest Linux-based supercomputer clusters to simultaneously identify relevant binding sites on protein disease targets and rapidly generate novel, drug-like, small molecules that bind specifically to those protein sites. In contrast to other computational approaches, the Locus technology requires only a high-resolution, 3-dimensional structure of the target protein to implement its drug discovery process. Presently, Locus Pharmaceuticals is synthesising and testing novel, computationally predicted, drug candidates for the treatment of debilitating and life-threatening human diseases including HIV/AIDS, cancer and inflammation.