[Chimera-users] questions on find hbond, find clashes/contact

[Elaine Meng]

Dear Hari,
Thanks so much for your kind words!  We try very hard to make useful  
tools and to answer everyone's questions.

(1) FindHBond.  I can't say exactly what happened without seeing your  
input and knowing each step you tried.  However, here are some  
guesses.  "inter-model" means between two different input files.  Did  
you open the two proteins from two different files?  If they are in  
the same file you should use "intra-model" (or "both") instead. Then,  
if you only want to look for H-bonds *between* the proteins, you could  
select one of the proteins and then set the option "Only find H-bonds  
with [exactly one end] selected."  FindHBond also has variable "Relax  
H-bond constraint" parameters, but the defaults ("Relax..." turned on,  
0.4 angstroms, 20 degrees) are generally reasonable.
Manual page:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/findhbond/findhbond.html

(2) Find Clashes/Contacts.  The meaning of your results depends on  
what values you use.  The manual page gives suggested ranges of values  
for finding "clashes" (unfavorable interactions where the atoms are  
too close together) and "contacts" (atoms within favorable interaction  
distances - thus all kinds of interactions, polar and nonpolar, plus  
the clashes):

"For detecting clashes, cutoff values of 0.4-1.0 Å and allowance  
values of 0.2-0.6 Å are generally reasonable (default criteria 0.6 and  
0.4 Å, respectively).

For detecting contacts, negative cutoff values of 0.0-(–1.0) Å with an  
allowance of 0.0 Å are generally reasonable (default contact criteria – 
0.4 and 0.0 Å, respectively)."

If you are using the graphical interface, you can just click the  
buttons "Default [clash]/[contact] criteria" to insert the default  
values, which are within the suggested ranges.  There is no single  
best number because it depends on the quality of your structure and  
for what purpose you are planning to use the results.  You have to use  
your judgement.  The quality of the results also depends on the  
quality of your input structure, not just on what numbers you use.   
However, in most cases, values in the suggested ranges are  
appropriate.  We use published VDW radii and have tried the values on  
many structures.  Just make sure you use the clash range if you want  
clashes, the contact range if you want contacts!  For publication  
purposes, you could just say you used this tool with recommended  
values to find contacts (or clashes).  It is not necessary to add  
hydrogens.
Manual page:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/findclash/findclash.html
VDW radii:
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/midas/vdwrad.html

For example, if I open 2gbp (glucose binding protein and glucose; does  
not have hydrogens), select ligand (glucose), click Designate, check  
against "all other atoms" and then use the default clash criteria,  
nothing is found.  There are no clashes with the glucose.  If I use  
the default contact criteria, there are 52 atom-atom contacts between  
the glucose and the binding protein.  I chose the option to "Select"  
the atoms.  Then Selection Inspector (Actions... Inspect) tells me  
that 14 residues and 39 atoms are selected.  If I deselect the glucose  
(command: ~sel ligand) then 13 residues and 27 atoms are selected.   
These are the protein residues and water residues interacting with the  
glucose.

If you are using values in the recommended range for clashes and get  
very many clashes, it may be that the docking program tends to put  
atoms close together.  That doesn't mean the program is bad, just that  
it generates approximate positions.

(3) There IS a minimization tool, see Tools... Structure Editing...  
Minimize Structure!  However, it may not meet your definition of user- 
friendly, and it is fairly slow. Calculations like minimization that  
involve force fields tend to be complicated because they involve many  
parameters, such as the size and charge of each atom.  You have to add  
hydrogens, but the tool will guide you through the process.  You might  
want to select as many atoms as possible to be "frozen" (held fixed)  
in place during the minimization. Fewer movable atoms makes the  
calculation faster.
Man page:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/minimize/minimize.html

As an alternative to minimization, you might want to take a look at  
the Rotamers tool (under Tools... Structure Editing).  With this tool  
you can see if different non-clashing conformations of the sidechains  
may be possible.  Using this would only be reasonable if there are  
only a few clashing side chains here and there, not a big cluster, and  
if backbone motion is not required.  Maybe you are already using the  
Rotamers tool to make your mutations!
Man page:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/rotamers/framerot.html

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                          meng at cgl.ucsf.edu
UCSF Computer Graphics Lab and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco
                      http://www.cgl.ucsf.edu/home/meng/index.html



On Apr 25, 2008, at 3:49 PM, Harinathachari Bahudhanapati wrote:

> Dear chimera support,
>                              I am a huge fan of chimera and I have so
> say I spend a lot of time on chimera these days, as a part of writing
> for my dissertation. I have a few questions and I sincerely you to
> request to help me out.
>
> 1. About findHbond: I never seem to get this one right. I model
> Enzyme-inhibitor complexes on patchdock. The inhibitor templates are
> either pdbs from rcsb or modelled on swissmodel. I am not able to
> locate or find any hbonds newly formed in the docked models, when I
> search for intermodel hbonds (I am looking for protein-protein
> interactions). Are there any special criteria or am I missing some
> thing? I want something similar to that of the output of HBPLUS (I
> never seem to get this working either - very frustrating)
>
> 2. About find clashes: What are the ideal parameters for clashes and
> contacts. I tried several things, they give me several no of overlaps
> for several different parameters. Are these vanderwaals interactions?
> because some times I see more than 40 interactions between two  
> residues
> -i.e., between the atoms of Enzyme and inhibitor? How reliable are
> these interactions (I need to publish my data) This tool does not seem
> to work unless I add hydrogens to both the chains.
>
> 3. It would be great, if there was a energy minimization tool in
> chimera because I introduce mutations. Please kindly suggest me if
> there are any easy to use tools for this. I tried COOT and
> swisspdbviewer, but not really that user-friendly.
>
> I read all the newsletter e-mails from CHIMERA users-list everyday.
> Thanks to Elaine, tom, eric and conrad. You guys rock..
> sincerely
> Hari
> hbahudha at fau.edu