Conformational Ensembles from Experimental Data and Computer Simulations

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Conformational Ensembles from Experimental Data
and Computer Simulations Poster Abstracts
157
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 Lee2, Minkyung Baek2 , Sangwoo Park2, Choak Seok2, Matthias Buck1,2.
1Case Western Reserve University, Cleveland, OH, USA, 2Seoul 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, S2 , 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