title: Measuring the shapes of macromolecules - and why it matters.
abstract: The molecular basis of life rests on the activity of biological macromolecules, mostly nucleic acids and proteins. A perhaps surprising finding that crystallized over the last handful of decades is that geometric reasoning plays a major role in our attempt to understand these activities. In this paper, we address this connection between geometry and biology, focusing on methods for measuring and characterizing the shapes of macromolecules. We briefly review existing numerical and analytical approaches that solve these problems. We cover in more details our own work in this field, focusing on the alpha shape theory as it provides a unifying mathematical framework that enable the analytical calculations of the surface area and volume of a macromolecule represented as a union of balls, the detection of pockets and cavities in the molecule, and the quantification of contacts between the atomic balls. We have shown that each of these quantities can be related to physical properties of the molecule under study and ultimately provides insight on its activity. We conclude with a brief description of new challenges for the alpha shape theory in modern structural biology.
authors.affiliation: Genome Center, University of California, Davis, 451 Health Sciences Drive, Davis, CA 95616, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Graduate Group of Applied Mathematics, University of California, Davis, 1, Shields Ave, Davis, CA, 95616, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Mach
authors.affiliation: Department of Computer Science and Genome Center, University of California, Davis, 1, Shields Ave, Davis, CA, 95616, United States.
authors.forename: Patrice
authors.initials: P
authors.lastname: Koehl
keywords: alpha shape; atomic contacts; ligand binding sites; proteins; solvation energy