Peptides are short chains (sequences) of naturally-occurring amino acids. They are found in all living cells and tissues, where they perform vital biological functions. Peptides are now being considered for use in nanotechnology as they are able to assemble to form a variety of nanostructures - nanofibers, nanosheets, and nanoparticles. Such structures have potential applications in a wide variety of fields including medicine, electronics, enzyme catalysis and drug release. The goal of this project is to develop an open software toolkit that enables the identification of peptide sequences that are capable of assembling into user-selected fiber-like structures. Users will be able to screen potentially thousands of peptide sequences that assemble into the nanostructure of their choosing, and rank order them according to their stability. An algorithm, PepAD (Peptide Assembly Design) will be developed that searches for sequences that assemble into structures specified by the user. An accompanying software package will allow further analysis of the relative speed at which a large number of these peptide sequences form the desired structure. To establish efficacy and a basis for future improvement of computational tools, selected designs will be validated experimentally using advanced biophysical characterization techniques and solid-state nuclear magnetic resonance spectroscopy. PepAD will be open source and easy to run. Its use by the developers and by members of the scientific and engineering communities should lead to the ability to design the next generation of complex nanostructures. The toolkit, which will be the first of its kind for these types of assemblies, will be available on GitHub and on the NSF-sponsored Molecular Simulation and Design Framework (MoSDeF).
Many peptides are known to adopt beta strand conformations and assemble spontaneously into a variety of nanostructures--- nanofibers, nanosheets, nanoparticles, etc. - with applications in a wide variety of fields including nanomedicine, electronics, drug release, and hydrogels. The goal of this project is to develop an open software toolkit that enables the identification of peptide sequences that are capable of assembling into user-selected beta-sheet-based structures. An algorithm, PepAD (Peptide Assembly Design) will be developed that searches for sequences that assemble into structurers specified by the user. PepAD will allow users to screen potentially thousands of peptide sequences that assemble spontaneously into the structure of their choosing, and rank order them according to their stability. Discontinuous molecular dynamics (DMD) simulation software along with the PRIME20 force field will also be made available to enable analysis of the designed structures? assembly kinetics. To establish efficacy and a basis for future improvement of computational tools, selected designs will be validated experimentally using biophysical characterization techniques and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. There are four objectives: (1) develop an algorithm, PepAD, that identifies short peptide sequences that are capable of self-assembling into user-determined amyloid structures; (2) perform DMD/PRIME20 simulations to examine assembly kinetics, (3) synthesize and test the peptide designs using biophysical characterization experiments and ssNMR, and (4) community test and refine the PepAD software and then install it on GitHub and on MoSDeF as a plugin. The toolkit, which will be the first of its kind for beta-sheet assemblies, will be open source and easy to use. Successful implementation of this software will pave the way for the computational design of nanostructures that self-assemble: (a) in response to a trigger such as a change in temperature, pH, or specific ions, and (b) when the peptides are conjugated to functionalities like small molecules, recognition elements, fluorophores or enzymes. Outreach activities include the creation of a video for general audiences that describes how molecular-level computer simulations can be used in the design of new materials and an iPad app that allows users to computationally design model proteins and then watch movies of them as they fold. The project will use the concept of harnessing self-assembly and related ideas to design educational activities for undergraduate STEM students. The project will work to broaden opportunities for women and minorities, and to increase science awareness in K-12 students.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
