News

Biodesy article cited as one of the most popular in 2015

Biodesy’s article, “Protein Conformational Changes Are Detected and Resolved Site Specifically by Second-Harmonic Generation” published in Biophysical Journal was announced as one of the most popular articles in the journal in 2015 at the Biophysical Society meeting.

Events

Webinar: Featured Speaker – Professor Frank McCormick, UCSF. “Identifying Allosteric Modulators of KRAS using the Biodesy Delta”. Register now

May 04, 2017

The K-Ras gene is mutated in 20-30% of all human cancers, accounting for about one million cancer deaths per year worldwide. Mutated K-Ras proteins have been deemed un-druggable because they do not contain pockets or active sites that can be exploited by traditional medicinal chemistry. However, recent advances in chemical biology have enabled new approaches to targeting K-Ras. One of these approaches harnesses an optical phenomenon known as Second Harmonic Generation (SHG) in a technique that is extremely sensitive to small changes in orientation of a protein relative to a membrane surface and can measure conformational change in real-time. We have built and optimized a robust SHG assay to screen for compounds that cause allosteric changes in K-Ras. In a screen of an ~2,800 fragment library we have identified compounds that bind to K-Ras in a GTP-dependent or GDP-dependent manner and promote distinct conformational changes in the protein. We hope that these fragments will; i) reveal novel allosteric binding pockets for drug targeting and, ii) prove to be useful tools for studying the relationship between K-Ras conformation and its biological functions.