StructureMan: A Structure Manipulation Tool to Study Large Scale Biomolecular Interactions.

Studying biomolecular interactions is a crucial but challenging task. Due to their large scales, many biomolecular interactions are difficult to be simulated via all atom models. An effective approach to investigate the biomolecular interactions is highly demanded in many areas. Here we introduce a Structure Manipulation (StructureMan) program to operate the structures when studying the large-scale biomolecular interactions. This novel StructureMan tool provides comprehensive operations which can be utilized to study the interactions in various large biological systems. Combining with electrostatic calculation programs such as DelPhi and DelPhiForce, StructureMan was implemented to reveal the detailed electrostatic features in two large biological examples, the viral capsid and molecular motor-microtubule complexes. Applications on these two examples revealed interesting binding mechanisms in the viral capsid and molecular motor. Such applications demonstrated that the StructureMan can be widely used when studying the biomolecular interactions in large scale biological problems. This novel tool provides an alternative approach to efficiently study the biomolecular interactions, especially for large scale biology systems. The StructureMan tool is available at our website: http://compbio.utep.edu/static/downloads/script-for-munipulation2.zip.

The Roles of Electrostatic Interactions in Capsid Assembly Mechanisms of Giant Viruses.

In the last three decades, many giant DNA viruses have been discovered. Giant viruses present a unique and essential research frontier for studies of self-assembly and regulation of supramolecular assemblies. The question on how these giant DNA viruses assemble thousands of proteins so accurately to form their protein shells, the capsids, remains largely unanswered. Revealing the mechanisms of giant virus assembly will help to discover the mysteries of many self-assembly biology problems. Paramecium bursaria Chlorella virus-1 (PBCV-1) is one of the most intensively studied giant viruses. Here, we implemented a multi-scale approach to investigate the interactions among PBCV-1 capsid building units called capsomers. Three binding modes with different strengths are found between capsomers around the relatively flat area of the virion surface at the icosahedral 2-fold axis. Furthermore, a capsomer structure manipulation package is developed to simulate the capsid assembly process. Using these tools, binding forces among capsomers were investigated and binding funnels were observed that were consistent with the final assembled capsid. In addition, total binding free energies of each binding mode were calculated. The results helped to explain previous experimental observations. Results and tools generated in this work established an initial computational approach to answer current unresolved questions regarding giant virus assembly mechanisms. Results will pave the way for studying more complicated process in other biomolecular structures.