Structural Genomics (SG) projects have now solved 15,000 new protein structures and most of these are of unknown or uncertain biochemical function. Here we present a powerful approach based on computed chemical properties of the individual residues in a protein structure. Local arrays of predicted active residues for sets of proteins of known function are matched with those of SG proteins. For instance, a superfamily consists of proteins with similar structure but multiple different kinds of biochemical function, including different types of reactivity as well as different substrate specificities. Each functional type has a different set of active amino acids. Typically active residues include those in the first layer that make direct contact with the substrate molecule(s) and also some residues in the second and third layers that play supporting roles in the catalytic process. Graph Representation of Active Sites for Prediction of Function (GRASP-Func) establishes local arrays of predicted residues that are common to proteins of the same function. Predicted local arrays for each SG protein are aligned against those of the known members of each functional family. Cases of predicted misannotation, where our prediction differs from the originally assigned function, are especially interesting. Experimental testing is performed by direct biochemical assays to test our predictions. For instance, we show that our predictions are confirmed that RV0760c from <i>Mycobacterium tuberculosis </i>has ketosteroid isomerase activity, whereas NP_103587.1 from <i>Mesorhizobium loti </i>does not. Some cases involving local site matches across different fold types for glycoside hydrolases are also presented.

Chemical properties for predicting protein function

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.