Practicum 2 - Getting used to force field


Appreciate differences between different minimization processes and force field parameters

Appreciate differences in methods for minimizing system and time scale for MM calculations.

 The system:

We will work on the  chromophore of the antiobiotic antitumor protein: Neocarzinostatin(Kim et al.). Prior to get into calculations, look at the structure and understand its molecular nature as much as you can like in practicum 1. Go to the Protein Data Bank and search for a holo form of the NCS (pdb 1O5P or 1nco). Open the holo-NCS pdb in Chimera. Look at the general fold of the protein and identify the structure of the chromophore. 

Minimization with force field approaches inside Chimera

!! to have all the functions required by this tutorial, you'll need a recent version of the program. Here few infos for its installation (only for linux).

1. Download the program (daily build). Generally, the downloaded program should be in Baixades (Downloads) 

2. Open a terminal (in ubuntu, in the desktop menu, look for terminal - konsole or gnome-terminal should appear)

3. In the terminal, go to the directory where the program has been downloaded (i.e. cd Baixades)

4. change the mode of execution of the file: chmod 755 name_chimera_version

5. then execute the file: ./name_chimera_version

6. type enter for all the questions

7. to execute program, go to the directory of installation (i.e. cd $HOME/.local/UCSF-chimera_version/bin/)

8. then execute it: ./chimera


Open UCSF chimera

To perform the minimization, we'll use a novel extension we developed in our group. Go to Tools/ MD/Ensemble Analysis/Molecular Dynamics Simulation

After the teacher explains the interface, go to the MD Options tab and untick Equilibration and Production phases. Then in the Minimization tab ask for 10000 Steepest descent steps put 0 to the conjugate gradient. 

Then go to the Running tab and put 4 processors for the run (Use multiple procs ticked and 4 in the entry line)

Then click run at the bottom of the interface.

 The first time you run the calculation, you will have several windows that will pop up and that are related to the set up of the force field for the molecule. This means that you will generate the parameters of the atoms, add the hydrogen and so on. 

Save the mol2 file of the minimized structure.

Exercise: Play a bit around the different SD and CG values in performing the minimization. Look at the value of the gradient and the energy in the reply log. Also look at the time it takes to complete the run. Repeat inversing the number of steps of CG and SD. 

Geometry optimization of the NCS chromophore with Gaussian and different approaches

Prepare a mol2 file that only includes the chromophore into it. In case we move towards QM/MM calculations. Then prepare a gaussian input following the teacher advices and perform a minimization using the PM6 semi empirical calculations. On your own, repeat the calcultion using a pure force field (Dreiding or UFF) and a pure quantum (DFT like B3LYP or HF) method. Compare the time needed for the calculations to end. Look at the more important geometric features of the optimized system and compare from one type of calculation to another. You may need to send calculations over night for the most costly approaches.

Careful: the QM calculations will last so you may loose the scratch file over night. Do the following:

1. save the input file from gaussview in a given location in your computer (i.e. /root/

2. run /opt/g09/g09 <> Sugar_free.log &

 Once you have QM calculations performed with one MM, one ab initio and one DFT method compare:

times, energy and geometries with the different methods. Then compare your results with those obtained by your classmates and try to dress some tendencies relative with the concepts exposed during the lessons.


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