Thursday, May 11, 2017

Small molecule energy minimisation and conformational search using Tinker

In this post I outlined the (possible) need for conformational analysis using a continuum model. Anders Christensen reminded me that Tinker can do this so I looked in to it. This blogpost and this GitHub repo were particularly helpful.  Here's what I found.

Generating atomic charges
Tinker has MMFF force field parameters except the atomic charges.  These can be generated from an sdf file using sdf2tinkerxyz (which relies on OpenBabel). When you download from SourceForge you get a bin file, which I didn't know what to do with so I downloaded the Linux executable from here instead.

./sdf2tinkerxyz -k default.key < xxx.sdf

creates yyy.xyz (coordinates) and yyy.key (charges), where yyy is the title in the sdf file (which I'll assume = xxx in the following). "default.key" is a file with Tinker keywords that is added to xxx.key. Here's mine

# Solvation Model
SOLVATE GBSA


#Force Field Parameters
PARAMETERS /opt/tinker/tinker/params/mmff.prm


Energy minimisation
To isolate the effect of continuum solvation on the pKa predictions, I want to generate conformers with RDKit and minimise them with MMFF/GBSA using Tinker.  This is done by

/opt/tinker/tinker/bin/minimize xxx.xyz -k xxx.key 0.01 > xxx.tout

"0.01" is the convergence criterium (in kcal/molÅ??). xxx.tout contains the energy information and a xxx.xyz_2 file is generated with the optimized coordinates.  This is in a format that OpenBabel can't handle, so I need to write a converter.  The main challenge is to translate the atom types into names. See the list called lookup in this code.

Conformational Search using SCAN
Tinker also has its own conformational search method. It looks like it's based on eigenvector following but I haven't looked closely at it yet.  This is done by

/opt/tinker/tinker/bin/scan xxx.xyz -k xxx.key 0 10 20 0.00001 > xxx.tout

Here I use the settings used in the DP4 GitHub repo.  "0" is automatic selection of torsional angles, "10" is the number of search directions (modes?), "20" is the energy threshold for local minima,and "0.00001" is the optimisation convergence criterium.  You get a bunch of coordinate files and xxx.tout holds the energy information.

I haven't really played with this option yet. If you have any tips, please leave comment.


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