Novel Applications for Natural Move Monte Carlo Simulations: From Protein Complexes to Nanomachines
My research revolves around the sampling of structural conformations of protein complexes and molecular machines. For this purpose I use the MOSAICS software package (Minary 2007) to perform Hierarchical Natural Move Monte Carlo simulations (Sim 2012). This method makes use of a combination of complexity reducing concepts with the aim to make molecular modeling of large complexes and their structural changes tractable. Key features include multicanonical sampling protocols, 3pt representation
and the use of knowledge potentials (Minary 2008). In addition we decompose our structures into groups of residues that are known or expected to move in concert "naturally". Sampling along these pre-defined degrees of freedom results in an ensemble of structures that can be represented by probability distributions that describe the "event space". Clustering of the structures subequently provides us with possible candidates for alternative conformers. Current work revolves around MHC complexes. In due course I will move on to larger proteins and nanomachines such as antibodies, the proteasome and the chaperonin. <br><br> References:<br>
Minary, P., 2007. MOSAICS versions [-3.9]. Available at: http://www.cs.ox.ac.uk/mosaics.<br>
Minary, P. & Levitt, M., 2008. Probing protein fold space with a simplified model. Journal of molecular biology, 375(4), pp.920–33.<br>
Sim, A.Y.L., Levitt, M. & Minary, P., 2012. Modeling and design by hierarchical natural moves. Proceedings of the National Academy of Sciences of the United States of America, 109(8), pp.2890–5.