Computational Molecular Design - Shaping Protein Conformations and Predicting Functional Sequences
Abstract
We develop foundational computational design methods to engineer proteins and protein interactions with altered and new functions [1-3]. Recently, we have shown that a new approach, borrowing mathematical formulations from the field of robotics, predicts and remodels protein conformations in proteins with high accuracy [4]. I will describe advances in these methods and their application to more accurately model protein conformational changes, as well as to predict and design protein interaction specificity. Experimentally, we utilize these molecular design predictions to characterize and control the action of proteins in cellular systems.
References
[1] Mandell, D.J. & Kortemme, T. (2009). Computer-aided design of functional protein interactions. Nature Chemical Biology, 5:797-807.
[2] Kortemme, T, Joachimiak, LA, Bullock, AN, Schuler, AD, Stoddard, BL. & Baker, D. (2004). Computational redesign of protein-protein interaction specificity. Nature Structural Molecular Biology 11, 371-379.
[3] Humphris, E.L. & Kortemme, T. (2007). Design of multi-specificity in protein interface. PLoS Computational Biology 3(8): 1591-1604.
[4] Mandell, D.J., Coutsias, E.A. & Kortemme, T. (2009). Sub-Angstrom Accuracy in Protein Loop Reconstruction by Robotics-Inspired Conformational Sampling. Nature Methods 6:551-2.
