Integrative Structural Bioinformatics: The Sculptor Modeling Software

Abstract

Integrative modeling techniques promise to deliver new insight by fusing data from multiple sources. Especially the docking of atomic models into low- to intermediate resolution volumetric data from cryo-electron microscopy has grown into an established technique over the last decade. In recent years the field has expanded and targets now also macromolecular systems that undergo large-scale conformational changes and models those also using data from various biophysical sources.Although the results reported so far indicate a wide-spread applicability, the development of integrative modeling techniques on the other hand also leads to new challenges. The size and complexity of the multi-scale data sets is extremely diverse and demands novel strategies not only for the modeling approaches but also regarding pre- and post-processing and visualization. We propose a series of new modeling and analysis techniques, tailored towards handling of heteroneous data sets - heterogeneous in size, level of detail, resolution and conformation. To overcome the challenges, an interactive peak search approach is presented, coarse graining is employed to efficiently model conformational differences, and new programmable graphics cards are used to efficiently render the resulting, time-varying atomic models. The new methods are embedded in an interactive visualization tool termed Sculptor, forming together a flexible, robust and versatile interactive modeling tool. The present report highlights also the overall concept and implementation of Sculptor. Sculptor is freely available from http://sculptor.biomachina.org and can be downloaded as package for Linux, Windows and MacOSX.This work was supported by NIH grant R01GM62968, by a grant from the Gillson Longenbaugh Foundation, and by startup funds of the University of Texas Health Science Center at Houston.