A Ligand-observed Mass Spectrometry Approach Integrated into the Fragment Based Lead Discovery Pipeline

A Ligand-observed Mass Spectrometry Approach Integrated into the Fragment Based Lead Discovery Pipeline

In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially f...

The Proteome Discovery Pipeline – A Data Analysis Pipeline for Mass Spectrometry-Based Differential Proteomics Discovery

Proteomics approaches enable interrogation of large numbers of proteins to provide a more comprehensive understanding of biological systems. High throughput proteomics typically utilizes liquid chromatography – mass spectrometry technology for data acquisition. Bioinformatic analysis tools are essential to manage and mine resulting high volume proteomics data sets. Data analysis is a current bo...

Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery.

In fragment-based drug discovery, the weak affinities exhibited by fragments pose significant challenges for screening. Biophysical techniques are used to address this challenge, but there is no clear consensus on which cascade of methods is best suited to identify fragment hits that ultimately translate into bound X-ray structures and provide bona fide starting points for synthesis. We have be...

Fragment - based Lead Discovery

Native Mass Spectrometry in Fragment-Based Drug Discovery.

The advent of native mass spectrometry (MS) in 1990 led to the development of new mass spectrometry instrumentation and methodologies for the analysis of noncovalent protein-ligand complexes. Native MS has matured to become a fast, simple, highly sensitive and automatable technique with well-established utility for fragment-based drug discovery (FBDD). Native MS has the capability to directly d...