Macromolecular structure visualization: a look at the applications that provide graphical interface to structure analysis. Part IV VMD.
A detour into Molecular Dynamics.
Instead of the regular conclusion I want show a few things that can be done with MD.
1) Simulate the effect of the protonation state of a few histidine residues on their ability to bind a Zn atom.
In the first video we have a zinc atom (charge 2+) surrounded by three histidine residues (each a 1+ charge). Watch as the similar charge eject the zinc from the spot t initially occupied!
Now, the same but with neutral histidines:
Now the zinc not only remains in place but you can see other residues changing orientation to better suite the charge!
2) The previous example was done by using energy minimization. MD allows for a longer scale work. For example, simulating a protein with a loop stabilized by a zinc atom bound to three deprotonated cysteines (and a "stable" water molecule):
You can even see a few water molecules sporadically binding to the zinc.
Since this last example was done with VMD I'll finish here. Next time I'll go into details of how this movie was generated with VMD.
The previous installments on these review series have focused on end-user GUI to 3D structure analysis and visualization. As I was getting ready to tackle the fourth I realized that the suite I wanted to review was actually geared towards molecular dynamics simulations. For a review and many applications of molecular dynamics and other computational methods I recommend this link: http://www.ncbi.nlm.nih.gov/pubmed/20513755
NB. Some of these links might require subscriptions to access full text. However, abstracts should be available to all.
Thus, I set to run a few simulations using GROMACS (a.k.a. Groningen Machine for Chemical Simulations). This MD suite is my favorite due to its availability (OS X, Linux, Windows, etc.), its price (free) and ease of use. By now GROMACS is fairly mature and robust. The website (a wiki by now) has grown in resources both from the programmers and contributors as well as from the users. In fact, the more I think about it there are few things I can say here that haven’t been said before.
For those that don’t know what molecular dynamics are a good simple description would be:
MD are the use of Newtonian classical mechanics to describe the motion of atoms.
Since the focus of this post is just a review I’ll follow the usual pattern, ease of use, available features and overall strengths and weaknesses. Be aware that I’ll show more than a bit of bias. For more details on MD check the GROMACS manual.
GROMACS ease of use.
Let’s start this section with a bitter pill: GROMACS is command-line only. That means that almost all interaction between the user and the software is through text. Commands like the following are the norm:
This commands is just the first one to convert a simple PDB into a more complex topology. By the way, follow the link to check a very good tutorial/test of how use GROMACS.
However, most of the data produced by GROMACS can be plotted or visualized. Visualization can be done with…, you guessed, VMD.
There are many good tutorials of how to get started with GROMACS that I am hard pressed to say it is not easy to use. The manual too is full of info both theoretical and practical. It might be at first but once you get going you start thinking about the important thing: How can I use GROMACS to do science.
Available features.
Current GROMACS version (4.5.3) offers the following force fields:
1: AMBER03 force field (Duan et al., J. Comp. Chem. 24, 1999-2012, 2003)
2: AMBER94 force field (Cornell et al., JACS 117, 5179-5197, 1995)
3: AMBER96 force field (Kollman et al., Acc. Chem. Res. 29, 461-469, 1996)
4: AMBER99 force field (Wang et al., J. Comp. Chem. 21, 1049-1074, 2000)
5: AMBER99SB force field (Hornak et al., Proteins 65, 712-725, 2006)
6: AMBER99SB-ILDN force field (Lindorff-Larsen et al., Proteins 78, 1950-58, 2010)
7: AMBERGS force field (Garcia & Sanbonmatsu, PNAS 99, 2782-2787, 2002)
8: CHARMM27 all-atom force field (with CMAP) - version 2.0
9: GROMOS96 43a1 force field
10: GROMOS96 43a2 force field (improved alkane dihedrals)
11: GROMOS96 45a3 force field (Schuler JCC 2001 22 1205)
12: GROMOS96 53a5 force field (JCC 2004 vol 25 pag 1656)
13: GROMOS96 53a6 force field (JCC 2004 vol 25 pag 1656)
14: OPLS-AA/L all-atom force field (2001 aminoacid dihedrals)
15: [DEPRECATED] Encad all-atom force field, using full solvent charges
16: [DEPRECATED] Encad all-atom force field, using scaled-down vacuum charges
17: [DEPRECATED] Gromacs force field (see manual)
18: [DEPRECATED] Gromacs force field with hydrogens for NMR
I love the fact that the force fields include their citations! That means you can head over to PubMed and look up the relevant reference. There you would learn why AMBER has evolved from Amber94 to Amber99SB-ILDN.
Besides many force field options (and the necessary solvent options) GROMACS allows for the addition of ions and everything you need to run a simulation. GROMACS also contains a big array of tools to analyze the results. Even better, it offers templates and details of the files produced so anyone can code a tool to analyze the data!
Every single program includes the related bibliographic references to the method of analysis.
Most of the output files are either text that can be plotted (data in ascii format) or pdb (or other structure-related format) that can be visualized.
Overall strengths and weakness.
I see GROMACS as one of the most readily available, easy to use MD suite. I always recommend it.
The only weakness I have faced is the use of non-protein/non-DNA molecules (for some details read this). That is not a GROMACS limitation but is in fact a difficulty faced by anyone doing MD of non-standard molecules.
Conclusion.
Molecular dynamics are the gateway to function based on structure.
Instead of the regular conclusion I want show a few things that can be done with MD.
1) Simulate the effect of the protonation state of a few histidine residues on their ability to bind a Zn atom.
In the first video we have a zinc atom (charge 2+) surrounded by three histidine residues (each a 1+ charge). Watch as the similar charge eject the zinc from the spot t initially occupied!
Now, the same but with neutral histidines:
Now the zinc not only remains in place but you can see other residues changing orientation to better suite the charge!
2) The previous example was done by using energy minimization. MD allows for a longer scale work. For example, simulating a protein with a loop stabilized by a zinc atom bound to three deprotonated cysteines (and a "stable" water molecule):
You can even see a few water molecules sporadically binding to the zinc.
Since this last example was done with VMD I'll finish here. Next time I'll go into details of how this movie was generated with VMD.
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