Columbia University

Technology Ventures

A tool for the modeling of conformational changes in proteins and other lager macromolecules

Technology #2631

Lead Inventor: Wayne A. Hendrickson, PhD

Tech Ventures Reference: IR 2631

A software tool for determining the structures and conformational changes of proteins using a virtual atom molecular mechanics force field

The function of many proteins is dependent on conformational transitions between different structural states. In order to fully understand the mechanisms of protein function, there is a need to better elucidate these transitions both experimentally as well as through modeling. Due to the complexities of these transitions, which can involve a wide range of interactions, computational modeling has often not been possible. This technology, virtual atom molecular mechanics (VAMM) force field, is an approach for using molecular mechanics calculations to model interactions within the protein structure. Using this system, the process of predicting protein conformational changes can be simplified sufficiently to feasibly perform modeling while still providing accurate results.

Accurate modeling of protein and macromolecule conformational changes that has been experimentally verified

This technology uses crystallographic data along with a virtual atom model that can accurately model the various conformations and geometries of a protein as it fluctuates from its native state. The effectiveness of this technology in modeling these conformational changes has been demonstrated through the correct prediction of the transition trajectory of adenylate kinase.

Applications:

• Predict conformational changes of protein structures in order to guide laboratory research. • Assist in drug discovery by offering insight into the binding mechanisms of potential drugs and their targets. • Modeling of other macromolecules such as DNA, RNA, and other polymers.

Advantages:

• This technology has been experimentally verified on adenylate kinase. • Technology can be packaged into a software tool for modeling proteins.

Licensing Status: Available for licensing and sponsored research support

Related Publications:

• W.A. Hendrickson, A. Korkut. A force field for virtual atom molecular mechanics of proteins. PNAS. Vol. 106, Issue 37. Sep. 2009. pp. 15667-15672. • W.A. Hendrickson, A. Korkut. Computation of conformational transitions in proteins by virtual atom molecular mechanics as validated in application to adenylate kinase. PNAS. Vol. 106, Issue 37. Sep. 2009. pp. 15673-15678.