The overall goal of this project is to develop a computational frame work to study energetics and assembly of viruses and supra molecular assemblies in general. The developed tools will be made available for the scientific community through the internet (World Wide Web) and personal communication as part of the service and dissemination. Towards this goal, we have revised our programs and procedures such that they would receive/send the data from/to the client/user via the internet. We are very close to linking the server to the MMTSB home page, where these tools can be accessed by the community at large. The server is setup such that the user would provide information/data of the protein of interest and selects the preferred mode of analysis. Various analysis tools include 1) estimation of association energies based on simple buried surface areas and atomic solvation parameters 2) computation of association energies based on the free energies of solvation using continuum electrostatics 3) calculation of residue-wise contributions of individual residues to binding energies 3) obtain an assembly pathway for a given set of association energies and 4) identify and tabulate all the possible non covalent interactions between inter subunit contacts that are found in a given virus capsid. All the above calculations will be done in the batch-mode in the order they are received on the computers obtained for the use of MMTSB project. The results will be returned to the user through electronic mail. Using the above tools, we are planning to analyze and catalogue the results for all the virus structures that are available in the protein data bank (PDB) and make them accessible on the WWW. The 'bottle neck' of such an analysis has been to identify and orient the viral protein structures in one of the conventional orientations, such that standard icosahedral operators can be applied to generate the symmetry partners, which is mandatory for the calculation of assembly pathways. To expedite such an analysis we propose to hire a summer student, who will (be trained to) retrieve and orient the virus structures into one standard orientation. Having such a 'preprocessed' data base of structures would facilitate, immensely, the ability to do the various analysis. We are also planning on improving the algorithms used in the programs and presentation of the results in such a way that would speedup the analysis and makes them easy to use. The work describing the model development and this representation of virus assembly interface energetics is described in the manuscript: Energetics of Quasi-equivalence: Computational Analysis of Protein-Protein Interactions in Icosahedral Viruses. V. S. Reddy, H. A. Giesing, R. T. Morton, A. Kumar, C. B. Post, C. L. Brooks, III and J. E. Johnson, Biophysical J., 74, 546-558 (1998). Structural Studies of Noda and Tetraviruses. J. Johnson and V. Reddy. In: The Insect Viruses, (ed.) L. Miller, L. Ball, Plenum, New York, in press (1998).
| Salmon, Loïc; Ahlstrom, Logan S; Horowitz, Scott et al. (2016) Capturing a Dynamic Chaperone-Substrate Interaction Using NMR-Informed Molecular Modeling. J Am Chem Soc 138:9826-39 |
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| Ahlstrom, Logan S; Law, Sean M; Dickson, Alex et al. (2015) Multiscale modeling of a conditionally disordered pH-sensing chaperone. J Mol Biol 427:1670-80 |
| Taylor, Kenneth A; Feig, Michael; Brooks 3rd, Charles L et al. (2014) Role of the essential light chain in the activation of smooth muscle myosin by regulatory light chain phosphorylation. J Struct Biol 185:375-82 |
| Zeng, Xiancheng; Chugh, Jeetender; Casiano-Negroni, Anette et al. (2014) Flipping of the ribosomal A-site adenines provides a basis for tRNA selection. J Mol Biol 426:3201-3213 |
| Vashisth, Harish; Skiniotis, Georgios; Brooks 3rd, Charles Lee (2014) Collective variable approaches for single molecule flexible fitting and enhanced sampling. Chem Rev 114:3353-65 |
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