100
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.
