SI2-SSE: Software Tools for Biomolecular Free Energy Calculations

TECHNICAL SUMMARY

The Office of Cyberinfrastructure, Division of Materials Research, Chemistry Division, and Division of Civil, Mechanical, and Manufacturing Innovation contribute funds to this award made on a proposal to the Software Infrastructure for Sustained Innovation solicitation. This award supports the development of a new set of software tools for calculating biomolecular free energies, transition paths, and reaction rates that will be based on and will augment the PIs' ABMD/REMD/SMD suite of codes. New capabilities are to be added to the existing codes, which should greatly enhance the applicability of the software to challenging biomolecular problems. In particular, the PIs aim to implement and develop: (i) the capability for dealing with dynamically coupled multiple walkers or replicas for enhanced sampling; (ii) the introduction of Transition Path Theory and Sampling methodology for calculating reaction rates and related physical quantities; and (iii) the introduction of the 'string method' for multi-dimensional free energy calculations and the calculation of the important minimum free energy path. These software tools will be released under the open source GPL, and released as part of the AMBER software package. The codes will also be released as stand-alone modules via the web for other users to integrate into their own programs.

To test and showcase the workings of the software package, the PIs will apply these methods to biomolecular systems where changes in handedness play an important role, including: proline-rich systems, mainly collagen and a new class of cell-penetrating peptides, and DNA and RNA in B and Z double helices.

This award will also enhance education through: the mentoring and recruitment of minority students, the development of a Biophysics option, the integration of research topics into current educational forums, working with local schools, and the development of a new Institute for Computational Science and Engineering.

NON-TECHNICAL SUMMARY

The Office of Cyberinfrastructure, Division of Materials Research, Chemistry Division, and Division of Civil, Mechanical, and Manufacturing Innovation contribute funds to this award made on a proposal to the Software Infrastructure for Sustained Innovation solicitation. This award supports the development of a new set of software tools that will enable the calculation of rates of chemical reactions involving biomolecules. The codes will also be able to calculate the energy that can be converted into useful work in a biochemical system. The codes will be distributed through a widely used software package called AMBER which contributes to the software cyberinfrastructure of computational chemistry, biochemistry, chemical engineering, materials, and biological physics communities. It will enable a wide range of computational research involving biological molecules. Among the possible applications are the study of the structure and transformations of biomolecules which provides information on their possible functions, the simulation of antibiotics, and simulating nanoscale technology applications.

This award will also enhance education through: the mentoring and recruitment of minority students, the development of a Biophysics option, the integration of research topics into current educational forums, working with local schools, and the development of a new Institute for Computational Science and Engineering.