MOSCOW, August 26. /TASS/ Scientists from Moscow Institute of Physics and Technologies (MIPT), the Institute of Biomedical Chemistry, the Institute for Energy Problems of Chemical Physics, and the Research Institute of Physico-Chemical Medicine have presented an algorithm to detect mutant proteins in cells, as reported by the press service of MIPT. The results of the study have been published in the journal Proteomics.
Occasional changes of amino acids in proteins caused by DNA mutations may result in changing protein functioning in cells. Some changes could also lead to cancer development. Studying mutant peptides will help to detect weaknesses in tumor cells and to search for more effective drug treatments.
The mass spectrometry is the main method of searching for mutant proteins. By means of this technique, the scientists define the molecular weight and composition of protein fragments. To analyze and identify the mutant protein, a special software compares the collected fragmentation data with the database containing all peptides of an organism.
However, this approach is not entirely suitable for proteins that are not encoded in a reference genome. To cope with it, the researchers have developed an algorithm which makes use not only of a database of proteins but also of databases of the genome of studied cells. The scientists have completed the protein "dictionary" with the sequences altering from the initial one by one or several amino acids which upgrade the search engine to disclose "wrong" proteins.
As a proof of concept, the researchers have used the database of genomic variants of HEK-293 (Human Embryonic Kidney 293) taken from a human embryonic kidney. HEK-293 cells are widely applied in cell biology research for many years because of their reliable growth and many possible mutations which are good prerequisites for testing the new approach.
With the data obtained in course of analysis, the scientists have defined which proteins and fragments are in the cells. Using the new approach, 113 unique peptide sequences in HEK-293 have been found in cells. Some of the discovered mutations had previously been proven to be connected with different types of cancer. The scientists hope that the new approach will help in future studies of tumor protein composition and in developing remedies to cope with mutant proteins of tumor cells.