A PCA-guided Search Algorithm to Probe the Conformational Space of the Ras Protein
Rudy Clausen, Amarda Shehu · 2013
We present an algorithm to probe the conformational space of Ras, a critical enzyme that employs conformational switching for its biological activity. The algorithm is guided by experimental data on crystallographic structures of wildtype and mutant Ras. A principal component analysis (PCA) over these structures provides search directions, which are used in combination with energetic refinement to sample low-energy conformations of Ras. Our results show that experimental structures are reproduced, and the space is further populated with novel structures, warranting further investigation into structural characterization of Ras.