Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I

47-POS Board 47 Investigating the Relationship between Characteristics of Protein-Protein Interfaces and Binding Affinity Gözde Kar 1 , Ayşe Derya Cavga 1 , Nilay Karahan 1 , Banu Özkan 2 , Attila Gürsoy 1 , Özlem Keskin 1 . 1 Koc University, Istanbul, Turkey, 2 Arizona State University, Tempe, AZ, USA Relating structure to function has been a fundamental issue in structural biology. Knowledge of structural details of protein-protein interactions is crucial in understanding protein function. However, to determine whether a protein complex actually exists under a given pH, temperature and concentration, and whether it is permanent or transient, knowledge of binding affinity is essential. Here, using a structure-based benchmark, we investigate whether the binding affinity correlates with the structural features of protein-protein interfaces. Proteins forming larger interfaces are observed to show a stronger binding, i.e. higher binding affinity. Additionally, higher number of critical residues, hot spots, implies a protein-protein interface with higher affinity. We also extend the contact order concept to analyze protein complexes and find that contact order of protein complexes correlate with binding affinity independent of the contact order of their unbound components. Finally, we investigate the organization of hot spot residues at protein-protein interfaces of benchmark complexes which show a large conformational change upon binding. Although protein interfaces undergo a large conformational change, there are some rigid residues which correspond to the computational hot spots at protein interfaces. Our findings would be crucial for predicting binding affinity based on features of protein interfaces as well as for docking studies.

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