[Chimera-users] SDF partial charges

[Elaine Meng]

Hello,
An additional follow-up to Nancy's question from Jan 31.
<http://www.cgl.ucsf.edu/pipermail/chimera-users/2010-January/004754.html 
 >

Daily builds (version 1.5) dated Feb 4 or newer will now automatically  
read the partial charges in 3D SDF files obtained directly from the  
PubChem database.
<http://pubchem.ncbi.nlm.nih.gov/release3d.html>

However, I wanted to caution everybody that the protonation states of  
the resulting molecules are not what you would expect at physiological  
pH.  The functional groups that would generally be charged near pH 7  
are neutralized, at least from the few examples that I've examined:   
carboxylic and other acids fully protonated rather than formally  
negative, aliphatic amines neutral rather than formally positive.  For  
example, alanine is given as H2N-CH(CH3)-COOH rather than + H3N- 
CH(CH3)-COO -

If that is the case for all of the 3D SDFs obtained directly from  
PubChem (Nancy, you may want to take a closer look at a sample of your  
structures), I would not recommend them for docking.  Instead, you may  
want to get small molecule structures from some place that has  
attempted to put them in reasonable charge states, such as the ZINC  
database.
<http://zinc.docking.org/>

Best,
Elaine
-----
Elaine C. Meng, Ph.D.
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco