Pages

Friday, June 17, 2011

Fast Calculation of van der Waals Volume as a Sum of Atomic and Bond Contributions

I was recently asked about a volume descriptor in Bioclipse, which is not yet available. Jmol can calculate surfaces, so that was my first thought. However, I then ran into a paper from 2003 by Zhao, called Fast Calculation of van der Waals Volume as a Sum of Atomic and Bond Contributions and Its Application to Drug Compounds (doi:10.1021/jo034808o).

The paper presents a very simple mathematical model, which approximates the molecular volume by a sum of atomic contributions, and a three terms to correct for atom-atom overlap, via the number of bonds, and corrections based on the number or aromatic and non-aromatic rings. The paper is clearly written, and the mathematics simple.

One problem with the publication though, are the numbers in the main text. They are wrong. I started of using the coefficients of the equations presented in the paper, but very soon ran into problems when I was writing up unit tests based on the volumes for compounds given as examples. In fact, the numbers in the main text are internally inconsistent. Not good. I believe it is partly caused by rounding, but that does not correct for the differences fully.

Fortunately, the Excel sheet in the supplementary information has the exact numbers, and those are numerically consistent.

The paper has been cited 46 times now, so, a fast volume descriptor seems relevant indeed. I am not sure how fast it will propagate to Bioclipse, as I do not have time soon to update the CDK version of Bioclipse (the major part of which is to ensure the Bioclipse-JChemPaint editor does not get broken, again).

Another thought about this paper, is that it is using the evil aromaticity concept, where the authors forgot to mention when they consider a ring to be aromatic.

Zhao, Y., Abraham, M., & Zissimos, A. (2003). Fast Calculation of van der Waals Volume as a Sum of Atomic and Bond Contributions and Its Application to Drug Compounds The Journal of Organic Chemistry, 68 (19), 7368-7373 DOI: 10.1021/jo034808o