Prediction of Complex Molecule Structures with HDX Mass Spectrometry-guided Molecular Dynamics Simulations Part II – Generalization and Parametrization

Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is a powerful emerging experimental technique which provides important information about the solvent exposed area of complex molecular systems that is not readily available through existing technologies. HDX-MS can be applied to the specific cases of small molecules binding to protein systems, which is very important for the understanding, and new design, of therapeutic compounds, including chemotherapeutic cancer drugs. However, the HDX-MS technique does not provide high-resolution atomic information which is a major inadequacy of the method. The standard computational chemistry techniques of Molecular Dynamics (MD) simulation gives exactly the high-resolution structures required. Using MD simulations guided by HDX-MS data, a method for the production of high-resolution structures based on HDX-MS data is being developed. The research in this internship, in partnership with MDS Analytical Technologies, a leading global supplier of life sciences tools, will take a previously-developed framework for the MD simulations and generalize it for new application to the set of all standard proteins.

Evan Kelly
Faculty Supervisor: 
Dr. Mariusz Klobukowski