This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A. Objectives Large scale finite element continuum solvation and electrostatics calculations will be performed to understand the role of charge-charge interactions at capsid inter-subunit interfaces during viral maturation. The results from this analysis will be used to computationally predict the effects of mutations at capsid subunit interfaces to be tested through experimental studies. In particular, we propose the following specific objectives: 1. Model the influence of charge interactions in Nudaurelia Omega (N?V) and Bacteriophage HK97 virus maturation through pKa prediction and continuum electrostatic calculations. 2. Integrate our electrostatic modeling framework into a large-scale characterization of viral electrostatics in the VIPERdb to develop new features for viral structure analysis (http://viperdb.scripps.edu/) [1]. The proposed objectives build on existing experimental work in the Johnson lab on N?v [2- 11] and HK97 [12-25] as well as past research by McCammon, Baker, and others [26, 27] which used the NBCR-supported tools APBS (http://apbs.sf.net/) [28] and PDB2PQR (http://pdb2pqr.sf.net/) [29, 30] to explore capsid electrostatics in viral maturation. However, this collaborative project will significantly extend the scope of this work through the new finite element mesh generation technology [31] provided by the NBCR-supported tool FETK (www.fetk.org/) [32] and its integration with APBS.
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