Restricted mobility of side chains on concave surfaces of solenoid proteins may impart heightened potential for intermolecular interactions

Significant progress has been made in the determination of the protein structures with their number today passing over a hundred thousand structures. The next challenge is the understanding and prediction of protein–protein and protein–ligand interactions. In this work we address this problem by analyzing curved solenoid proteins. Many of these proteins are considered as “hub molecules” for their high potential to interact with many different molecules and to be a scaffold for multisubunit protein machineries. Our analysis of these structures through molecular dynamics simulations reveals that the mobility of the side‐chains on the concave surfaces of the solenoids is lower than on the convex ones. This result provides an explanation to the observed preferential binding of the ligands, including small and flexible ligands, to the concave surface of the curved solenoid proteins. The relationship between the landscapes and dynamic properties of the protein surfaces can be further generalized to the other types of protein structures and eventually used in the computer algorithms, allowing prediction of protein–ligand interactions by analysis of protein surfaces . Proteins 2015; 83:1654–1664. © 2015 Wiley Periodicals, Inc.