Calculation of rigid-body conformational changes using restraint-driven Cartesian transformations

Biophysical Journal
P SompornpisutE Perozo

Abstract

We present an approach for calculating conformational changes in membrane proteins using limited distance information. The method, named restraint-driven Cartesian transformations, involves 1) the use of relative distance changes; 2) the systematic sampling of rigid body movements in Cartesian space; 3) a penalty evaluation; and 4) model refinement using energy minimization. As a test case, we have analyzed the structural basis of activation gating in the Streptomyces lividans potassium channel (KcsA). A total of 10 pairs of distance restraints derived from site-directed spin labeling and electron paramagnetic resonance (SDSL-EPR) spectra were used to calculate the open conformation of the second transmembrane domains of KcsA (TM2). The SDSL-EPR based structure reveals a gating mechanism consistent with a scissoring-type motion of the TM2 segments that includes a pivot point near middle of the helix. The present approach considerably reduces the amount of time and effort required to establish the overall nature of conformational changes in membrane proteins. It is expected that this approach can be implemented into restrained molecular dynamics protocol to calculate the structure and conformational changes in a variety of membr...Continue Reading

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Citations

Sep 30, 2009·Chemical Reviews·Ivet BaharIndira H Shrivastava
May 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Bertrand VilenoPiotr G Fajer
Feb 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yufeng ShenJianpeng Ma
Jun 11, 2015·Chemical Biology & Drug Design·Kanon SujareePornthep Sompornpisut
Jul 1, 2005·FEBS Letters·Juan Manuel AriasEdward Perez-Reyes
Aug 28, 2004·Journal of Molecular Graphics & Modelling·Kay-Eberhard Gottschalk
Apr 4, 2014·Nature Communications·Olivier DalmasEduardo Perozo
Sep 5, 2001·Nature Reviews. Neuroscience·G E FlynnW N Zagotta
Feb 2, 2021·European Biophysics Journal : EBJ·Michael SchmidtKay Hamacher

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