Electrostatic Potential Map - Ligand Docking

  • Knowledge of the electrostatic potential map of complexes of lanthanides is important in studies of ligand docking.
     
  • In this tutorial, you will learn how to draw the electrostatic map around a lanthanide complex.
     
  • To perform this task, you will need the following softwares: MOPAC2012, and Gabedit.
     
  • This tutorial uses version 2.4.0 of GABEDIT. If you installed a different version of GABEDIT, the commands you will have to use may differ from the ones appearing below.
     
  • As an example, let us consider the complex BAFYUD [(Acetylacetonato)-bis(nitrato-O,O')-(2,2':6',2''-terpyridine)-neodymium(iii)], below:

    bafyud gabedit lanthanide neodymium
     

  • First draw and optimize the geometry of your complex following the instructions in Drawing Complexes.
     
  • If you run into any problems, please review the warning in the bottom part of the tutorial Drawing Complexes.
     
  • As an example, we provide the file bafyud.mop.
     
  • Warning: make sure you have used the AUXkeyword in first line of your .mop file, otherwise an .aux file will not be created.
     
  • You should now have the corresponding .aux file. As an example, we provide the bafyud.aux
  • After completion of the calculation, open the Gabedit and click on “Display Geometry/Orbitals/Density/Vibration” button: . This will open a new window called “Gabedit: Orbitals/Density/Vibration”.
     
  • Right click on the black screen and choose the option “Orbitals” in the menu that appears. Select the option “Read geometry and orbitals from a Mopac aux file”. A new window will appear, from which you will navigate until you find your .aux file and click Open.
     
  • The complex structure will appear, as well as a new window with information about the orbitals (which may be closed because it is not needed). As an example, below we present the structure of BAFYUD:

    bafyud lanthanide neodymium

  • Notice that in this case, no bonds appear coordinating the neodymium ion. That is because the bond connection algorithm of GABEDIT may not always work efficiently with some high coordination number lanthanide complexes. Every now and then, some coordinating bonds may not appear, while sometimes some other spurious bond connections may also appear. However, the positions of the atoms are always correct.
     
  • Right click on the black window and choose “MEP” > “Using Molecular Orbitals” > “MEP by solving Poisson Equation using Multigrid Method”.
    A new window “Calculation of MEP from Molecular Orbitals/Poisson by Multigrid”, will open.
    If you wish, you may increase the "Number of points" to improve image quality. However, a larger number of points will substantially take more CPU time to run. At first, leave the number of points at its default value of 65.
    Click on "OK".
     
  • Gabedit will start computing the electrostatic potential around the molecule. Be patient! The progress of the calculation can be checked on the left bottom part of the screen.

    gabedit
     

  • When the calculation ends, a new window "Calculations of isosurfaces..." appears. You must set a value for the isosurface of the electrostatic potential map. The default value which appears may or may not generate an adequate surface. Please, remember that smaller values will generate larger surfaces and vice-versa. At first you can accept the suggested value which appears on the small window and click OK.
     
  • As an example, below we present the electrostatic map around BAFYUD using a isosurface value of 0.4:

    bafyud isosurface neodymium
     

  • The negative parts of the isosurface will appear blue and the positive parts red (according to the litmus test convention).
     
  • If you would like to change the value of the isosurface, you can do that easily without having to recompute the grid. Right click anywhere on the window and choose "Surfaces" > "reset isovalue". Choose a new isovalue and wait - it will take a while for the new isosurface to be computed and drawn.

    isovalue window gabedit
     

  • The electrostatic map isosurface of positively charged lanthanide complexes tend to appear all blue - and that is normal, because its overall positive charge dominates the grid, especially at larger distances (smaller isosurface values). The above complex is overall neutral, and that is why it easily presents two distinct positive (red) and negative (blue) regions, respectively, regions of Lewis acidity and basicity, colored according to the litmus test convention. 
     
  • To delete the isosurface, right click anywhere on the window and choose "Surfaces" > "delete all".