Journal of Computer-Aided Molecular Design

, Volume 29, Issue 11, pp 1025–1034

Extracting ligands from receptors by reversed targeted molecular dynamics


DOI: 10.1007/s10822-015-9863-2

Cite this article as:
Wolf, R.M. J Comput Aided Mol Des (2015) 29: 1025. doi:10.1007/s10822-015-9863-2


Short targeted MD trajectories are used to expel ligands from binding sites. The expulsion is governed by a linear increase of the target RMSD value, growing from zero to an arbitrary chosen final RMSD that forces the ligand to a selected distance outside of the receptor. The RMSD lag (i.e., the difference between the imposed and the actual RMSD) can be used to follow barriers encountered by the ligand during its way out of the receptor. The force constant used for the targeted MD can transform the RMSD lag into a strain energy. Integration of the (time-dependent) strain energy over time yields a value with the dimensions of “action” (i.e, energy multiplied by time) and can serve as a measure for the overall effort required to extract the ligand from its binding site. Possibilities to compare (numerically and graphically) the randomly detected exit pathways are discussed. As an example, the method is tested on the exit of bisphenol A from the human estrogen-related receptor \(\gamma\) and of GW0072 from the peroxysome proliferator activated receptor.


Reversed targeted MD Nuclear receptors Ligand exit pathways 

Supplementary material (490 kb)
Supplementary material 1 (pdf 491KB)

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Novartis Institutes for Biomedical Research, NIBRNovartis Pharma AGBaselSwitzerland

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