Adenylate Kinase Potential of Mean Force

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

In 2009, we studied the conformational transition between open and closed E. coli AdK without substrate, i.e. “apo AdK”, with a variety of computational methods.² As part of the study we also produced a free energy landscape (a potential of mean force or PMF) as a function of two collective variables, the angles formed by the LID and NMP domains with the CORE domain.³ We ² and others^4,5 have used this PMF to compare methods that sample transition paths to the underlying free energy landscape.

Terms of Use

The data are made available under a Attribution-ShareAlike 4.0 International licence (include the following when using the data):

Adenylate Kinase Potential of Mean Force 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.

When you make use of the data (contained in the file free_bw2_tol1e-05.dat) in published work, cite the paper²

O. Beckstein, E. J. Denning, J. R. Perilla, and T. B. Woolf. Zipping and unzipping of adenylate kinase: Atomistic insights into the ensemble of open ? closed transitions. J. Mol. Biol., 394(1):160–176, 2009.

Data

The file free_bw2_tol1e-05.dat contains the PMF data shown in Fig. 4a of the JMB paper².

The image shows the data plotted with cubic spline smoothing.

File format

free_bw2_tol1e-05.dat is the output from WHAM. The important data columns are

1. NMP-core angle (degrees)
2. LID-core angle (degrees)
3. free energy in kcal/mol

(Other columns are output from wham and can be ignored.)

Methods

Conformations of E. coli 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’s wham code with

• bin size 2º
• tolerance of the self consistency procedure 1e-5 kT
• limits 34º < NMP < 80º and 94º < LID < 156º

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

References

1. S. L. Seyler and O. Beckstein, O. Sampling large conformational transitions: adenylate kinase as a testing ground. Mol. Simul., 40(10–11): 855–877, 2014.
2. O. Beckstein, E. J. Denning, J. R. Perilla, and T. B. Woolf. Zipping and unzipping of adenylate kinase: Atomistic insights into the ensemble of open / closed transitions. J. Mol. Biol., 394(1):160–176, 2009.
3. See the 2009 paper² for the definitions and the MDAnalysis tutorial’s Exercise 4 for Python code to calculate the angles.
4. M. Gur, J. D. Madura, and I. Bahar. Global transitions of proteins explored by a multiscale hybrid methodology: Application to adenylate kinase Biophysical Journal, 105(7):1643 – 1652, 2013.
5. A. Uyar, N. Kantarci-Carsibasi, T. Haliloglu, and P. Doruker. Features of large hinge-bending conformational transitions. Prediction of closed structure from open state. Biophysical Journal, 106(12):2656 – 2666, 2014