Principal Investigator: Jack Snoeyink
Funding Agency: National Institutes of Health (indirect Duke University)
Agency Number: 133612
This project consists of extension, modernization, and increased interoperability for the MolProbity web service and the related suite of software for analyzing 3D macromolecular structures, to further improve its user-friendliness, generality, robustness, speed, and future maintainability for the benefit of both the many current users and the even broader community of biomedical researchers who now wish to employ it. This system has two central aspects that are so far unique. One is the kinemage graphics concept that separates a human-editable text file of the hierarchical display list from a content-independent 3D graphics program (Mage or KiNG) that displays the kinemage with priority on smooth interactive performance, open-ended explorability, and optimized perception of 3D relationships. The second unique aspect is all-atom contact analysis, which uses detailed sterics of all optimized hydrogens to characterize inter- and intra-molecular contacts and to diagnose and correct most errors in experimental structure models. This system has been in wide use since 1992, growing by major enhancements. It is open-source and cross-platform (Mac/Windows /Linux/Unix/web browser), supporting structural biology, biochemistry, bioinformatics, educational, and even non-molecular uses. MolProbity had 11,500 serious working sessions this year, and the Protein Data Bank site now uses our validation and graphics tools. This project would allow the reorganization and documen-tation that cannot be justified as part of a laboratory research effort but which is essential to long-term viability and growth as an open resource. Support would be added for CIF format files, nucleic acids, NMR ensembles, and structure comparisons. Modularity, code re-use, object-oriented organization, and standard web-design practice would be improved. The interface and the underlying programs of the MolProbity service would be thoroughly reworked to enhance both turnkey simplicity for study of a single protein and powerful flexibility for expert structural-biology clients. Scripted command-line use, precalculated material, and software web access would be enhanced to serve a new group of prediction and bioinformatics users analyzing thousands of files. User feedback, collaborators, and our own testing in production mode will guide this process. This project is particularly relevant to public health in its goals of helping substantially to speed production of and to improve accuracy of molecular models for development of chemotherapeutics.