title: Restricted mobility of side chains on concave surfaces of solenoid proteins may impart heightened potential for intermolecular interactions.
abstract: 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.
authors.affiliation: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600 025, India.
authors.forename: L
authors.initials: L
authors.lastname: Ramya
authors.affiliation: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600 025, India.
authors.forename: N
authors.initials: N
authors.lastname: Gautham
authors.affiliation: Centre d'études d'agents Pathogènes et Biotechnologie pour la Santé, CNRS-FRE3689, 1919 Route de Mende, 34293 Montpellier, Cedex 5, France.|Institut de Biologie Computationnelle, 95 Rue de la Galéra, 34095, Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chaloin
authors.affiliation: University ITMO, Institute of Bioengineering, 197101, St. Petersburg, Russia.|Centre de Recherches de Biochimie Macromoléculaire, UMR5237 CNRS, Université Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France.|Institut de Biologie Computationnelle, 95 Rue de la Galéra, 34095, Montpellier, France.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kajava
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties
chemical_list: D008024:Ligands; D011506:Proteins
keywords: molecular dynamics; protein surface; protein-ligand interactions; side chains; solenoid proteins