The PI has developed a software suite, called MEAD, for calculations of electrostatic properties of proteins using continuum electrostatic models. MEAD is useful for the calculation of the ionization properties of sidechains, redox potentials of redox-active proteins, energetics of enzyme mecha- nisms, stability of proteins and protein-drug interactions. The NIH program announcement PAR-08-010, """"""""Continued Development and Maintenance of Software,"""""""" calls for proposals for the development and maintenance of ex- isting software that serves a biological community of users. The proposed project will do this in several ways. (1) Combination of the program with computational chemistry software making hybrid techniques available to a broad community that were heretofore available only in the research group of the PI and collaborators. (2) Optimization of MEAD for the new multi-core processors. (3) Improvements to MEAD's object-oriented library to open up its capabilities to a wider range of programmers, including programmers who prefer to program in high-level scripting languages, particularly Python. (4) The addition of new or improved improved molecular surface and en- ergy minimization capabilities. (5) Documentation and web resources to promote the continued growth and interactivity of the MEAD user commu- nity, and to help users outside the PI's group not only to use the programs, but to use the library to develop their own customized applications. MEAD has been, and will continue to be distributed on an open-source basis.
The MEAD software suite calculates electrostatic effects in protein mol- ecules, helping researchers understand the function of proteins of biomed- ical interest. It is also used to calculate protein-drug interactions for """"""""virtual screening,"""""""" in which potential drug molecules are evaluated computation- ally to narrow down the number of molecules needing costly experimen- tal tests. The proposed grant will support the continued development and maintenance of MEAD.
|Blachly, Patrick G; Sandala, Gregory M; Giammona, Debra Ann et al. (2015) Broken-Symmetry DFT Computations for the Reaction Pathway of IspH, an Iron-Sulfur Enzyme in Pathogenic Bacteria. Inorg Chem 54:6439-61|
|Gajewski, Stefan; Comeaux, Evan Q; Jafari, Nauzanene et al. (2012) Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I: a member of the phospholipase D superfamily. J Mol Biol 415:741-58|
|Han, Wen-Ge; Sandala, Gregory M; Giammona, Debra Ann et al. (2011) Mossbauer properties of the diferric cluster and the differential iron(II)-binding affinity of the iron sites in protein R2 of class Ia Escherichia coli ribonucleotide reductase: a DFT/electrostatics study. Dalton Trans 40:11164-75|
|Han, Wen-Ge; Giammona, Debra Ann; Bashford, Donald et al. (2010) Density functional theory analysis of structure, energetics, and spectroscopy for the Mn-Fe active site of Chlamydia trachomatis ribonucleotide reductase in four oxidation states. Inorg Chem 49:7266-81|