Surface Electrostatic Potential Per Residue
===========================================
Usually, the distribution of electrostatic potential around a protein
molecule is visualized by solving the Poisson-Boltzmann equation using a
grid base approach (`APBS `_/`Delphi
`_) and coloring the molecular
surface with the obtained electrostatic potentials, as shown below.
.. image:: /_static/surface_electrostatics.png
:align: center
This only allows for qualitative inspection of one structure or conformation
at a time. In contrast, MD DaVis can calculate the surface electrostatic
potential per residue from electrostatics calculations on a sample of
conformation from the MD trajectory. Thereby, incorporating dynamical
information into the analysis. The steps involved are as follows:
#. Obtain a sample of conformations from the trajectory as PDB files.
Ideally, all the conformations should be centered at the origin and
aligned. Optionally, the reference conformation used for alignment may be
oriented with its first, second and third `principal axis `_
along the x, y, and z axis, respectively. When comparing samples from
two or more trajectories ensure that the reference structures for each
are aligned to reduce discrepancy caused by grid selection during
electrostatics calculation.
#. Use ``md-davis electrostatics`` to run MSMS and DelPhi on each PDB file.
.. code-block::
md-davis electrostatics --surface -m -d -o [PDB_FILES]
This calculates the triangulated molecular surface using the
`MSMS `_ program
(`Sanner et al., 1996 `_) and evaluates the electrostatic
potentials at the vertices of the triangulated surface
using `Delphi `_
(`Li et al., 2019 `_). In addition,
the volumetric data for electrostatic potential at grid points around the
molecule are also saved by DelPhi in
`Gaussian CUBE format `_. This can be
used for 3D vislization of the surface electrostatic potentials (Figure
above) or :ref:`electric field dynamics `.
It is advisable to align the PDB files and specify the grid size for
Delphi calculation, so that the same grid points are used for each
calculation.
#. Specify the path to the directory containing the surface potential
files in the input `TOML `_ file used by
:ref:`:ref:`collate `.
.. code-block:: toml
[residue_property]
surface_potential = ''
#. The total and mean electrostatic potential per residue is calculated
when the data is :ref:`collated ` into an HDF file.
.. code-block::
md-davis collate input.toml
This will search for all ``.pot`` files in the specified
````. The vertices corresponding to each residue are
identified along with the corresponding electrostatic potential. The
total and mean of the electrostatic potentials on the vertices for each
residue are calculated. The total gives information about the charge on
the surface as well as the exposed surface area, while the mean
nullifies the contribution from the exposed surface area. The mean and
standard deviation of both are calculated and saved in the
output HDF file.
#. Follow the steps for creating a :ref:`residue property plot ` to visualize the data.
.. code-block::
md-davis plot residue output_residue_wise_data.p
.. note:: A discrepancy between the molecular surface calculated by MSMS and
the molecular surface used by DelPhi to detect the protein's interior
was observed for buried residues in multimeric proteins. DelPhi uses a
different dielectric constant for the molecule's interior, so the potential
on these residues was very high.
.. code-block:: bash
md-davis electrostatics --surface -m -d -o [PDB_FILES]
``md-davis electrostatics`` is a wrapper for running
`Delphi `_ and reporting
the electrostatic potential at the vertices of a triangulated surface obtained using
`MSMS `_. Therefore, these must
be installed for this command to work, which may be downloaded from
http://compbio.clemson.edu/delphi and
http://mgltools.scripps.edu/downloads#msms, respectively.
The default parameters used for running Delphi are:
* 2000 linear interations
* maximum change in potential of 10\ :sup:`-10` kT/e.
* The salt concentration is set to 0.15 M
* solvent dielectric value of 80 (dielectric of water)
If you want to use different set of parameters, you may run Delphi without
the md
The atomic charges and radii from the CHARMM force field are provided by
default. The parameter files containing the atomic charges and radii for
DelPhi are available at:
http://compbio.clemson.edu/downloadDir/delphi/parameters.tar.gz
The output potential map is saved in the cube file format (used by Gaussian
software); the other formats do not load in molecular visualization software.
The following charge and radius files are provided with the source code for
MD DaVis.
``md_davis/md_davis/electrostatics/charmm.crg``
``md_davis/md_davis/electrostatics/charmm.siz``
If you receive a warning during Delphi run regarding missing charge or
radius. Then the missing properties must be added to these files or
whichever files you provide to ``md-davis electrostatics``.
Electric Field Dynamics
=======================
The electrostatic potentials calculated in :ref:`guides/electrostatics:Surface Electrostatic
Potential Per Residue` can be visualized as a 3D animation of
electric field lines using:
.. code-block:: bash
md-davis electrodynamics --ss_color --surface --name Human_AcP 2VH7/2VH7_electrostatics
This creates a `PyMOL `_ session with the
conformations as frames in the animation as shown below:
.. image:: /_static/2VH7_electrodynamics.webp
1. The coordinates of the reference structure are translated to place the
center of mass of the molecule at the origin and rotated so that the first,
second, and third principal axes are along the x, y, and z-axes,
respectively.
2. The frames sampled from the trajectory are aligned to the reference.
3. The electrostatic potentials are obtained for each sampled structure
using Delphi. The box for each calculation is centered at the origin, and
the number of grid points is manually set to the same value for each
structure to ensure the same box size during each calculation.
4. The surface electrostatic potentials calculated per residue or atom are
written into the output PDB file's B-factor or occupancy column.
5. The output PDB file and the corresponding electric field from the sample
are visualized as frames in PyMOL (Schrödinger, LLC, 2015), which can
animate the dynamics of the electric field lines.