Method to Identify the Molecular Structure of Large Biomolecules via IM/MS

This method uses data derived from Ion Mobility-Mass Spectroscopy (IM/MS) to computationally decipher molecular structures of proteins, protein assemblies, and protein-small molecules interactions.

Advantages

• Enables high-throughput large-scale systematic fragment-based drug discovery
• Requires a fraction of the sample amounts and time
• Uses systems already available to most pharmaceutical and therapeutics companies.

Introduction and Applications

This technology has the potential to revolutionize the field of drug discovery, especially fragment-based drug discovery, by elucidating the molecular structure of biomolecules and any bound ligands with high fidelity. 

Currently, structural characterization in drug discovery is often undertaken with techniques such as x-ray crystallography, nuclear magnetic resonance, or cryo-EM. These traditional methods require significant sample amounts, purified samples, and are poorly suited for high-throughput screening assays. Further, many potentail targets are not amenable to structural characterization by these methods, including, for example, the soluble protein assemblies implicated as toxic agents in Alzheimer's or Parkinson's diseases.

In contrast, the current method exhibits sufficient sensitivity, sample-throughput, and dynamic range to enable the high-throughput, large-scale systemic screening of small molecule-target interactions. Additionally, the samples can be studied in a manner that more closely mimics their natural conditions, including flexible branches and glycan moieties that other methods often miss.

The Technology

The biomolecules of interest are analyzed in a few minutes via IM/MS. The output is then analyzed computationally, providing structural characterization. The program can be modified to work with in-house supercomputers or with cloud-based computing services, such as Amazon's AWS.

Click here to watch an interview with Dr. Bleiholder: https://www.youtube.com/watch?v=G7etpbzsWtg