Adenylate Kinase Potential of Mean Force

<p>Adenylate kinase (AdK) is a enzyme that undergoes a large hinge-like motion. Because of an abundance of structural and functional data, it has become a standard system to test computational methods for sampling conformational transitions.¹</p> <p>In 2009, we studied the conformational transition between open and closed <em>E. coli</em> AdK without substrate, i.e. &ldquo;apo AdK&rdquo;, with a variety of computational methods.² As part of the study we also produced a free energy landscape (a <strong>potential of mean force</strong> or <strong>PMF</strong>) as a function of two collective variables, the angles formed by the LID and NMP domains with the CORE domain.³ We ² and others⁴^,⁵ have used this PMF to compare methods that sample transition paths to the underlying free energy landscape.</p> <p><strong>Terms of Use</strong></p> <p>The data are made available under a <strong>Attribution-ShareAlike 4.0 International</strong> licence (include the following when using the data):</p> <p><em>Adenylate Kinase Potential of Mean Force</em> by O Beckstein, EJ Denning, JR Perilla, TB Woolf is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Based on a work at http://becksteinlab.physics.asu.edu/file_download/11/free_bw2_tol1e-05.dat.</p> <p>When you make use of the data (contained in the file free_bw2_tol1e-05.dat) in published work, <strong>cite</strong> the paper²</p> <p>O. Beckstein, E. J. Denning, J. R. Perilla, and T. B. Woolf. <em>Zipping and unzipping of adenylate kinase: Atomistic insights into the ensemble of open ? closed transitions</em>. J. Mol. Biol., 394(1):160&ndash;176, 2009.</p> <p><strong>Data</strong></p> <p>The file free_bw2_tol1e-05.dat contains the PMF data shown in Fig. 4a of the JMB paper².</p> <p>The image shows the data plotted with cubic spline smoothing.</p> <p>File format</p> <p>free_bw2_tol1e-05.dat is the output from WHAM. The important data columns are</p> <ol> <li>NMP-core angle (degrees)</li> <li>LID-core angle (degrees)</li> <li>free energy in kcal/mol</li> </ol> <p>(Other columns are output from wham and can be ignored.)</p> <p><strong>Methods</strong></p> <p>Conformations of <em>E. coli</em> AdK were umbrella-sampled in the space of the NMP-core and LID-core angles.³ The protein was modelled in implicit solvent with the ACE2 electrostatics model. The resulting umbrella data were unbiased using Alan Grossfield&rsquo;s wham code with</p> <ul> <li>bin size 2&ordm;</li> <li>tolerance of the self consistency procedure 1e-5 <em>kT</em></li> <li>limits 34&ordm; &lt; NMP &lt; 80&ordm; and 94&ordm; &lt; LID &lt; 156&ordm;</li> </ul> <p>The first 2000 frames (200ps) of each window were discarded as equilibration and the remaining 3000 frames were used for the PMF. For further details please see the paper.²</p> <p><strong>References</strong></p> <ol> <li>S. L. Seyler and O. Beckstein, O. <em>Sampling large conformational transitions: adenylate kinase as a testing ground</em>. Mol. Simul., 40(10&ndash;11): 855&ndash;877, 2014.</li> <li>O. Beckstein, E. J. Denning, J. R. Perilla, and T. B. Woolf. <em>Zipping and unzipping of adenylate kinase: Atomistic insights into the ensemble of open / closed transitions</em>. J. Mol. Biol., 394(1):160&ndash;176, 2009.</li> <li>See the 2009 paper² for the definitions and the MDAnalysis tutorial&rsquo;s Exercise 4 for Python code to calculate the angles.</li> <li>M. Gur, J. D. Madura, and I. Bahar. <em>Global transitions of proteins explored by a multiscale hybrid methodology: Application to adenylate kinase</em> Biophysical Journal, 105(7):1643 &ndash; 1652, 2013.</li> <li>A. Uyar, N. Kantarci-Carsibasi, T. Haliloglu, and P. Doruker. <em>Features of large hinge-bending conformational transitions. Prediction of closed structure from open state</em>. Biophysical Journal, 106(12):2656 &ndash; 2666, 2014&nbsp;</li> </ol>