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Biomolecular Flexibility Analysis

Team: Tom Madej (Team Lead), Sanjay Rathee, Lianna Khachikyan

What is the problem?

Proteins achieve their functionality via conformational changes. When a protein undergoes a cofnromational change, some parts may be relatively stable and the more flexible parts allow for adjustments to the structure, to enable its functions. We aim to use the huge amount of information in larger structure datasets to elucidate the relationships between rigidity and flexibility and the functions of molecular assemblies.

Why should we solve it?

The why to our project is best explained by Martin Karplus:

"Many allosteric proteins are, in fact, constructed from semi-rigid domains or subdomains with hindges and/or semi-rigid subunits, which can move relative to each other."

How do we plan to solve this?

Previously we have implemented programs to identify structurally conserved subdomains using datasets, that can be used to model the rigid and flexible regions. In this project we work out a prototype function to assess how the more flexible parts correspond to the different possible conformations of the structures. We end up with a program framework that can be easily modified to consider different methods to evaluate the relationships between the local rigidity/flexibility and the molecular conformations. With future software experiments we can use this framework to search for the most effective methods to provide important insights.