A Combined Molecular Dynamics, Rigidity Analysis Approach for Studying Protein Complexes

Proteins form complexes when they bind to other molecules, which is often accompanied by a conformation change in one or both interacting partners. Details of how a compound associates with a target protein can be used to better design medicines that therapeutically regulate disease-causing proteins. Experimental and computational techniques for studying the binding process are available, however many of them are time and money intensive, or are computationally expensive, and hence cannot be done on a large dataset. In this work, we present a hybrid, computationally efficient approach for studying the stability of protein complex. We use short Molecular Dynamics (MD) simulations to generate a small ensemble of protein-complex conformations, whose flexibility we then analyze using an efficient graph-theoretic method implemented in the KINARI software. For our dataset of proteins, we show that our combined MD-rigidity analysis approach provides information about the stability of the protein-complex that would not be attained by either of the two methods alone.