Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

120-POS Board 40 From Single Structures to Ensembles: Application of the Galaxy Program Suite to BPTI, Ubiquitin and the RBD of Plexin-B1; Validation Against NMR Data Gyu Rie Lee 2 , Minkyung Baek 2 , Sangwoo Park 2 , Choak Seok 2 , Matthias Buck 1,2 . 1 Case Western Reserve University, Cleveland, OH, USA, 2 Seoul National University, Seoul, South Korea. It is now widely accepted that an accurate representation of a protein structure should incorporate a description of internal as well as protein loop dynamics. Lindorff-Larsen and colleagues suggested that protein structures can be refined by NMR derived order parameters, S 2 , by including this measure and/or RDCs as an additional restraint in the refinement protocol[1]. More recently it has become clear that the amplitude of local motions can be predicted with considerable accuracy by considering the surrounding atoms and the packing environment they may provide[2]. Nevertheless, the prediction of loop motions, if not distinct loop conformations has remained a challenge. We apply here the Galaxy Suite of Programs (GalaxyLoop and GalaxyVoyage)[3] to several test-cases: BPTI and Ubiquitin, which have been extensively characterized by NMR spectroscopy well as by molecular dynamics simulations(e.g.[4,5]). For BPTI is was important to consider both disulphide bond chirality and internal water molecules, but good agreement with the predominant conformational states could be obtained. Ubiquitin motions emphasized small displacements, whereas the ubiquitin-like RhoGTPase Binding Domain has long loops inserted into an ubiquitin fold. Some of these loops undergo considerable motions on the ps-ns timescale as measured by NMR relaxation[6], which suggested the NMR derived structure needed substantial local refinement[7]. These examples suggest that the implementation of ensemble refinement into the Galaxy Suite of Programs should be successful. [1] Lindorff-Larsen K, et al,. Nature 2005 433:128-32 [2] Zhang F, Brüschweiler R. JAmChemSoc 2002 124:12654-5.

[3] Park H, et al. PLoSONE 2014 9: e113811. [4] Lange OF, et al., Science 2008 320:1471-5. [5] Shaw DE, et al., Science 2010 330:341-6. [6] Bouguet-Bonnet S, Buck M. JMolBiol. 2008 377:1474-87. [7] Tong Y, et al., Structure 2008 16:246-58

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