Mathematical model for empirically optimizing large scale production of soluble protein domains
1 Genomic Sciences Center RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan
2 Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
3 Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-0012, Japan
BMC Bioinformatics 2010, 11:113 doi:10.1186/1471-2105-11-113Published: 1 March 2010
Efficient dissection of large proteins into their structural domains is critical for high throughput proteome analysis. So far, no study has focused on mathematically modeling a protein dissection protocol in terms of a production system. Here, we report a mathematical model for empirically optimizing the cost of large-scale domain production in proteomics research.
The model computes the expected number of successfully producing soluble domains, using a conditional probability between domain and boundary identification. Typical values for the model's parameters were estimated using the experimental results for identifying soluble domains from the 2,032 Kazusa HUGE protein sequences. Among the 215 fragments corresponding to the 24 domains that were expressed correctly, 111, corresponding to 18 domains, were soluble. Our model indicates that, under the conditions used in our pilot experiment, the probability of correctly predicting the existence of a domain was 81% (175/215) and that of predicting its boundary was 63% (111/175). Under these conditions, the most cost/effort-effective production of soluble domains was to prepare one to seven fragments per predicted domain.
Our mathematical modeling of protein dissection protocols indicates that the optimum number of fragments tested per domain is actually much smaller than expected a priori. The application range of our model is not limited to protein dissection, and it can be utilized for designing various large-scale mutational analyses or screening libraries.