Samuel Demharter
Interests
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 functional motions in MHC complexes as well as the impact of epigenetic marks on nucleic acid structures.
References:
Minary, P., 2007. MOSAICS versions [-3.9]. Available at: http://www.cs.ox.ac.uk/mosaics.
Minary, P. & Levitt, M., 2008. Probing protein fold space with a simplified model. Journal of molecular biology, 375(4), pp.920–33.
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.
Selected Publications
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Modeling Functional Motions of Biological Systems by Customized Natural Moves
Samuel Demharter‚ Bernhard Knapp‚ C.M. Charlotte M. Deane and Peter Minary
In Biophysical Journal. Vol. 111. No. 4. Pages 710–721. August, 2016.
Details about Modeling Functional Motions of Biological Systems by Customized Natural Moves | BibTeX data for Modeling Functional Motions of Biological Systems by Customized Natural Moves | DOI (10.1016/j.bpj.2016.06.028) | Link to Modeling Functional Motions of Biological Systems by Customized Natural Moves
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Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo.
Bernhard Knapp‚ Samuel Demharter‚ Charlotte M Deane and Peter Minary
In Bioinformatics (Oxford‚ England). Vol. 32. No. 2. Pages 181–6. January, 2016.
Details about Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo. | BibTeX data for Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo. | DOI (10.1093/bioinformatics/btv502) | Link to Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo.
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Tuning Cytokine Receptor Signaling by Re−orienting Dimer Geometry with Surrogate Ligands
Ignacio Moraga‚ Gerlinde Wernig‚ Stephan Wilmes‚ Vitalina Gryshkova‚ Christian P. Richter‚ Wan−Jen Hong‚ Rahul Sinha‚ Feng Guo‚ Hyna Fabionar‚ Tom S. Wehrman‚ Peter Krutzik‚ Samuel Demharter‚ Isabelle Plo‚ Irving L. Weissman‚ Peter Minary‚ Ravindra Majeti‚ Stefan N. Constantinescu‚ Jacob Piehler and K. Christopher Garcia
In Cell. Vol. 160. No. 6. Pages 1196–1208. 2015.
Details about Tuning Cytokine Receptor Signaling by Re−orienting Dimer Geometry with Surrogate Ligands | BibTeX data for Tuning Cytokine Receptor Signaling by Re−orienting Dimer Geometry with Surrogate Ligands | DOI (10.1016/j.cell.2015.02.011) | Link to Tuning Cytokine Receptor Signaling by Re−orienting Dimer Geometry with Surrogate Ligands