title: Fractal Dimensions of Macromolecular Structures.
abstract: Quantifying the properties of macromolecules is a prerequisite for understanding their roles in biochemical processes. One of the less-explored geometric features of macromolecules is molecular surface irregularity, or 'roughness', which can be measured in terms of fractal dimension (D). In this study, we demonstrate that surface roughness correlates with ligand binding potential. We quantified the surface roughnesses of biological macromolecules in a large-scale survey that revealedDvalues between 2.0 and 2.4. The results of our study imply that surface patches involved in molecular interactions, such as ligand-binding pockets and protein-protein interfaces, exhibit greater local fluctuations in their fractal dimensions than 'inert' surface areas. We expect approximately 22 % of a protein's surface outside of the crystallographically known ligand binding sites to be ligandable. These findings provide a fresh perspective on macromolecular structure and have considerable implications for drug design as well as chemical and systems biology.
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland fax: (+41) 44 633 13 79.
authors.forename: Nickolay
authors.initials: N
authors.lastname: Todoroff
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland fax: (+41) 44 633 13 79.
authors.forename: Jens
authors.initials: J
authors.lastname: Kunze
authors.affiliation: Sanofi-Aventis Deutschland GmbH R&D Frankfurt am Main, Germany.
authors.forename: Herman
authors.initials: H
authors.lastname: Schreuder
authors.affiliation: Sanofi-Aventis Deutschland GmbH R&D Frankfurt am Main, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hessler
authors.affiliation: Sanofi-Aventis Deutschland GmbH R&D Frankfurt am Main, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Baringhaus
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland fax: (+41) 44 633 13 79.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
keywords: Computational chemistry; Drug discovery; Fractal; Ligand binding; Protein structure