If you want to have a broader understanding of the importance of the computational breakthrough described in a Nature Methods paper published today by UC San Diego researchers, then take a look at a paper published last friday in Science magazine.
The
Science Review highlighted the fact that the number of drugs from natural products is dropping even though there are vast numbers of untapped natural compounds that could lead to new drugs.
Below I have pasted a few reactions and parenthetical comments on this
Science paper from one of the co-lead authors on the
Nature Methods paper: Julio Ng, a doctoral student in Bioinformatics at UC San Diego.
Also, there is a cool underwater drug discovery photo of one of William Gerwick, one of the Nature Methods authors, here:
http://cse-ece-ucsd.blogspot.com/2009/07/algorithms-answer-hot-or-not-question.htmlThe link to the original press release is here:
http://www.jacobsschool.ucsd.edu/news/news_releases/release.sfe?id=866“The Science paper is very pertinent to our work. My impression is that the Science paper is an extended introduction of our paper, explaining the motivation of our work. Of course, we only attempt to automate the characterization of a set of natural products with a very specific structure (cyclic peptides). In the Science paper, they also discuss the potential of polyketides for commercial drugs. However, a main point of the paper is that drugs based on natural products seem to be declining in recent years. One of the reasons for this decline is that the model of natural product screening is not amenable to high-throughput screening (HTS). This is where we want to bring our software to help the high-throughput identification and dereplication of natural products. I really like the concluding sentence where the authors state that it is not that natural products are a dead end from drug discovery, far from it, they are a vast resource that remains unexplored. And I think we would like to provide the means to help achieve this end.”
-Julio Ng, a co-lead author on the Nature Methods paper and a doctoral student in Bioinformatics at UC San Diego.Some relevant quotes from the Science paper with added comments from Julio Ng, a co-lead author on the Nature Methods paper and a doctoral student in Bioinformatics at UC San Diego.
“A prevailing sentiment in many pharmaceutical organizations is that screening of natural product sources is a difficult effort with a high probability of duplication; that is, the result may be a known compound that cannot be patented.” (This is the problem of dereplication – Julio Ng)
[This is Daniel Kane typing now...the "problem of dreplicatioin" is one that the UC San Diego researchers tackled in their Nature Methods paper].“Clearly the biological resource is there, but access and examination are problematic, especially if there is pressure for a short time frame for discovery of new leads.” (I think mass spectrometry, coupled with computational tools can speed up this process significantly. Mass spectrometry itself has advantages of being high-throughput, require small quantities of the sample, the data is amenable to computational tools for analysis, etc –Julio Ng)
