The UHBD (University of Houston Brownian Dynamics) program is capable of solving the linear and non-linear Poisson-Boltzmann equation using a finite-difference method. In addition, the program can be used to perform Brownian dynamics simulations of the association of two molecules and of the internal dynamics of a protein. Steady and non-steady state rate constants of encounter of a molecule (e.g. substrate/inhibitor) with a target (e.g. enzyme) can be computed from the Brownian dynamics simulations. The UHBD code can also be used to perform stochastic dynamics calculations or molecular mechanics energy minimizations using Poisson-Boltzmann and/or other molecular mechanics forces. The program also has the ability to compute electrostatic free energies of binding for two molecules as well as non-electrostatic surface area dependent terms.

The aim of this tutorial is to compute the electrostatic potentials of 2 proteins, barnase and barstar, which bind to form a high-affinity complex. These proteins are also the subject of other tutorials of this practical. The same electrostatic potentials as computed here are used in the MolSurfer tutorial.

0. Make a new local directory and go there (e.g. type "mkdir uhbd ; cd uhbd").
Download the following files into this directory (Shift+left_mouse on the links, and save under the same names) :
uhbd1.pdb - coordinates of barnase prepared for uhbd calculations by adding polar hydrogen atoms
uhbd2.pdb - coordinates of barstar prepared for uhbd calculations by adding polar hydrogen atoms
uhbd.exe - uhbd executable
uhbd.inp - input script for uhbd
uhbd.qtable.dat - file, defining atomic charges and radii (OPLS parameter set)
Alternatively, copy the files using the command: cp /home/client1/data/uhbd* ./

To be able to execute the downloaded uhbd.exe file, type "chmod +x uhbd.exe"

1. Analyze files uhbd.qtable.dat, uhbd.inp, uhbd1.pdb and uhbd2.pdb.
- why does the first residue in uhbd1.pdb have 2 names ?
- which other residues in uhbd1.pdb have non-standard names ? (there are 2 more of these)
- what charge is assigned to the NH1 atom of residue Arg ? to NH2 atom of residue Arg ? (refer to uhbd.qtable.dat)
- what is the size of the grid (in Angstroms) over which the electrostatic potential will be computed?

2. Run uhbd calculation:
Type:
./uhbd.exe uhbd.inp uhbd.out

This calculation will take about 30 seconds.

3. Look at the 3 output files that appear in your directory.
- referring to the file uhbd.inp, try to figure out why the files uhbd1.grd and uhbd2.grd are so large and how one could make them 8 times smaller. (note that no protein atom should extend beyond the grid)
- browse the uhbd output file (uhbd.out) to find out what the net charges of barnase and barstar are.
- browse the uhbd output file to check if the NH1 atoms of Arg residues are indeed assigned charge of -0.8e.
- browse the uhbd output file to check if convergence of the electrostatic potentials was achieved and, if so, how many iterations were required.