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Interaction force diagrams: new insight into ligand-receptor binding

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Abstract

A method is described to calculate and visualize the interaction forces of ligand-receptor complexes. Starting from an X-ray crystallographic structure, a “thawing” procedure results in a force-field energy-minimized geometry which is close to the crystallographic starting point. By subtracting non-bonded interactions of the ligand with each amino acid residue and using the resulting force vectors to describe the slope of the remaining potential, two types of interaction force diagrams are created; the first shows the direction of the force vectors in 3D and the second shows the magnitude of the force vectors. The latter representation leads to definition of an ‘Interaction Force Fingerprint’ (IFFP) which is characteristic of the ligand-receptor binding. IFFPs are used to discuss ligand binding in the human estrogen receptors ERα and ERβ, and provide new insight into ligand selectivity between receptor isoforms.

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Notes

  1. PDB entries 1X7R, 1X7J [7].

  2. This program is freely available to MOE users at http://svl.chemcomp.com.

  3. Since it is difficult to visualize the 3D details of force vectors using the 2D images printed here, the original files for the figures discussed in this manuscript are provided as supplemental information. These files can be viewed with PyMol [20] which is freely available from www.pymol.org.

  4. Substitution Matrix: blosum 62 [25], penalties for gap start and gap length 7 and 1 respectively, iteration limit: 100 and failure limit: 10, Tree based method was used for initial estimate build up.

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Authors and Affiliations

  1. Department of Chemistry, Carleton University, Ottawa, Canada, K1S 5B6

    Hooman Shadnia, James S. Wright & James M. Anderson

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  1. Hooman Shadnia
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  2. James S. Wright
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  3. James M. Anderson
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Correspondence to Hooman Shadnia.

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Shadnia, H., Wright, J.S. & Anderson, J.M. Interaction force diagrams: new insight into ligand-receptor binding. J Comput Aided Mol Des 23, 185–194 (2009). https://doi.org/10.1007/s10822-008-9250-3

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