Regensburg 2013 – scientific programme
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BP: Fachverband Biologische Physik
BP 2: Proteins
BP 2.5: Talk
Monday, March 11, 2013, 10:45–11:00, H44
Integrating Genomic Information with Molecular Simulation for Protein Dynamics — •Alexander schug1, Hendrik Szurmant2, Martin Weigt3, and Abhinav Verma1 — 1Karlsruhe Institute of Technology — 2The Scripps Reserach Institute — 3Université Pierre et Marie Curie
Protein function often requires a protein to form a complex or adopt multiple conformations during its function cycle. Structural characterization of these states is experimentally difficult as they are typically stabilized by transient interactions. Here, we demonstrate how a mixed theory approach can predict such structures on the example of two-component signal transduction systems (TCS), a ubiquitous signal response system. We predicted the TCS complex structure in high agreement (3.5 RMSD) with concurrent experimental work [1] by combining molecular dynamics [2] and statistical genomic analysis [3]. Similarly, we were able to predict the active conformation occurring during autophosphorylation by identifying co-evolving interdomain amino acid pairs in agreement with biochemical mutagenesis data [3]. We can now simulate the conformational transition between active and inactive conformations, quantify its free-energy barrier and its change as reaction to transmembrane forces exercised by the sensor domain. [unpublished data]
[1] Schug A et al., PNAS (2009) 106, 22124-22129
[2] Schug A and Onuchic J, Curr Opin Pharm (2010) 10, 709-714
[3] Weigt M et al., PNAS (2009) 106, 67-72
[4] Dago A et al., PNAS (2012), 109, E1733-42