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.

DelPhiForce, a tool for electrostatic force calculations: Applications to macromolecular binding.

Long-range electrostatic forces play an important role in molecular biology, particularly in macromolecular interactions. However, calculating the electrostatic forces for irregularly shaped molecules immersed in water is a difficult task. Here, we report a new tool, DelPhiForce, which is a tool in the DelPhi package that calculates and visualizes the electrostatic forces in biomolecular systems. In parallel, the DelPhi algorithm for modeling electrostatic potential at user-defined positions has been enhanced to include triquadratic and tricubic interpolation methods. The tricubic interpolation method has been tested against analytical solutions and it has been demonstrated that the corresponding errors are negligibly small at resolution 4 grids/Å. The DelPhiForce is further applied in the study of forces acting between partners of three protein-protein complexes. It has been demonstrated that electrostatic forces play a dual role by steering binding partners (so that the partners recognize their native interfaces) and exerting an electrostatic torque (if the mutual orientations of the partners are not native-like). The output of DelPhiForce is in a format that VMD can read and visualize, and provides additional options for analysis of protein-protein binding. DelPhiForce is available for download from the DelPhi webpage at http://compbio.clemson.edu/downloadDir/delphiforce.tar.gz © 2017 Wiley Periodicals, Inc.