SAPH-ire analyzes existing data repositories of protein modifications and 3-D protein structures to help scientists identify and target research on “hotspots” likely to be important for biological function. Shown is the structural projection of PTM hotspots onto the 3-D structure of a heterotrimeric G protein. Regions of the protein that are modified are color coded to indicate observation frequency. Computer illustration: Torres Laboratory.
Modern mass spectrometry techniques have helped scientists identify more than 300,000 post-translational modifications (PTMs) in different families of proteins across numerous species. These PTMs come in many forms, resulting from the action of different enzymes, and are often indicators of how and where proteins contact one another to bring about different cell behaviors.
“Mass spectrometry is so effective that it has created an exponential curve in the knowledge of how proteins are modified,” said Matthew Torres, an assistant professor in the Georgia Tech School of Biology. “The rate at which we can detect new PTMs has now far surpassed the rate at which we can understand what they do from a classical biochemical approach. You have so much information that you don’t know where to begin.”
To address this issue, Torres and graduate students Henry M. Dewhurst and Shilpa Choudhury have developed and tested a new informatics technology that analyzes existing data repositories of protein modifications and 3-D protein structures to help scientists identify and target research on “hotspots” most likely to be important for biological function.
Known as SAPH-ire (Structural Analysis of PTM Hotspots), the tool could accelerate the search for potential new drug targets on protein structures and lead to a better understanding of how proteins communicate with one another inside cells.
“SAPH-ire predicts positions on proteins that are likely to be important for biological function based on how many times those parts of the proteins have been found in a chemically modified state when they are taken out of a cell,” Torres explained. “SAPH-ire is a tool for discovery, and we think it will lead to a new understanding of how proteins are connected in cells.”
The tool and its testing were reported in the journal Molecular and Cellular Proteomics. The research was supported by the National Institute of General Medical Sciences (NIGMS), which is part of the National Institutes of Health (NIH).—JOHN TOON