MODIFICATION
A -- Defense Sciences Research and Technology
- Notice Date
- 5/4/2004
- Notice Type
- Modification
- NAICS
- 541710
— Research and Development in the Physical, Engineering, and Life Sciences
- Contracting Office
- Other Defense Agencies, Defense Advanced Research Projects Agency, Contracts Management Office, 3701 North Fairfax Drive, Arlington, VA, 22203-1714
- ZIP Code
- 22203-1714
- Solicitation Number
- BAA04-12
- Response Due
- 2/2/2005
- Archive Date
- 3/3/2005
- Point of Contact
- Brett Giroir, Deputy Director, DSO, Phone (571) 218-4224, Fax (571) 218-4553,
- E-Mail Address
-
bgiroir@darpa.mil
- Description
- BAA04-12, Addendum 5 Special Focus Area: Protein Design Processes. Email: baa04-12@darpa.mil; DUE: September 17, 2004. The Defense Sciences Office is soliciting innovative research ideas in response to two technically challenging protein design problems: 1) creating the ability to make enzymes that catalyze chemical reactions not performed by natural enzymes for the synthesis of chemicals of interest to the Department of Defense demonstrated by designing a protein that catalyzes the regio- and chemo-specific nitration of phenol; 2) creating the ability to rapidly (hours as opposed to weeks or months) make new proteins that inactivate new biological pathogens or toxins demonstrated by designing, in less than one day, a protein that will specifically inactivate human influenza virus. The problems were chosen because: a) they are of interest to the DoD and national security; and, b) they require the creation of new and revolutionary computational and experimental tools whose development requires a concerted effort by an interdisciplinary team of scientists drawn from the fields of chemistry, math, physics and biology. Other protein design problems that are equivalent to or exceed the challenges posed here and that share the same critical features cited above would also be of interest to DARPA. This announcement is a call for proposals describing research that will radically change the way protein design is now practiced. Therefore, successful proposals will have to clearly identify the fundamental scientific and technical issues now faced by the protein design community and describe innovative and interdisciplinary approaches to overcoming current scientific and technical barriers that limit rapid protein design. It is expected that this research will be conducted in phases, with definitive near-, mid- and far-term milestones proposed over a 4-5 year period in order to provide measurable metrics for monitoring success toward this revolutionary and pervasive technology for designing functional proteins. Because of the complicated nature of this research, the submission of a white paper (pre-proposal) is STRONGLY recommended. The following sections provide background information about the research topic as well as detailed instructions for submitting white papers and proposals to the Protein Design Program. Background. Mature materials and sensor engineering technologies have emerged from fundamental knowledge in materials science, physics, chemistry, and mathematics. A critical factor limiting the maturation of biotechnology into a robust engineering discipline that can reliably design and manufacture biomaterials, biosensors and bioprocesses in support of DoD is the primitive state of computational tools for bioengineering in comparison to, say, electrical or mechanical engineering. A major barrier to developing practical computational tools for bioengineering is the inherent complexity of biological materials and systems. The creation of a robust, bottom-up (e.g., Current Opinion in Structural Biology. 13:490, 2003) protein engineering process would have a pervasive impact on biotechnology that would enable and accelerate the development of many new DoD applications (e.g., catalysts that enhance warfighter performance [nutrition, wakefulness], biosensors, underwater adhesives, biomotors) as well as many unanticipated technologies. A typical soluble protein might contain 20 different amino acid subunits in a 300 subunit-long sequence. Each amino acid contains 4-5 different elements (C, O, N, H and sometimes S). The smallest amino acid, glycine, has 10 atoms (MW=75), while the largest, tryptophan, has 23 atoms (MW=204). A typical 300 subunit-long protein thus contains thousands of atoms in a compact structure whose spatial extent is on the order of 10 nm on a side. Although our ability to accurately predict the structure of a protein with atomic resolution given only an amino acid sequence is steadily improving (PROTEINS: 23(5), 1995; Supplement 1, 1997; Supplement 3, 1999; Supplement 5, 2001; Supplement 6, 2003), we are interested in the inverse problem: specifying the amino acid sequences that will generate a desired and functional structure. Solutions to the inverse problem are currently not feasible and might even be NP-hard (Protein Engineering 15:779, 2002). Current approaches to protein design (Journal of Structural Biology 134:269, 2001) primarily involve either top-down approaches via the modification of known protein frameworks (Nature 423:185, 2003) or are limited to the design of protein scaffolds with hydrophobic cores and fixed backbones (Science 282:1462, 1998; Science 302:1364; 2003). If we are to design functional proteins of the kind specified by the challenge problems posed here, dramatic advances will need to be made in research areas that include, but are not limited to: optimization methods for searching through sequence and structure space; energy functions that are sensitive to local atomic structure and that explicitly handle van der Waals, solvation, electrostatics, and hydrogen bonding interactions; the incorporation of backbone flexibility and functional groups into protein design algorithms (this will be particularly important for enzyme design as one must design stable structures that are capable of substrate binding, catalysis and product release); use of knowledge-based and informatics approaches to represent and use secondary-structures and folds as composable elements; and loop or turn classification. We believe that major technical improvements in these and other research areas that contribute to protein design will emerge only through the concerted efforts of highly interdisciplinary research teams drawing on state-of-the-art capabilities in mathematics (e.g. geometry, topology, signal processing), physics (e.g., solid state, quantum mechanics), chemistry (e.g., chemical reaction pathways, chemical structure analysis), and biology (e.g., novel informatics-based approaches to protein structure classification). White Paper and Proposal Information. In order to minimize unnecessary effort in proposal preparation and review, proposers are strongly encouraged (but are not required) to submit white papers (pre-proposals) in advance of full proposals. White Paper Instructions. Please put the phrase Protein Design Process in the title of the white paper. White papers may address any combination of the research areas discussed above but those with a sole emphasis on informatics-based techniques are strongly discouraged. While DARPA does not participate or provide direction in the formation of research teams, in order to facilitate teaming opportunities for interdisciplinary work, DARPA is sponsoring a Teaming Website at the following URL: http://pdp.walcoff.com. Investigators can use this site to make others aware of their own capabilities and to identify capabilities they seek in potential teammates. The web site will also provide answers to frequently posed questions regarding the solicitation. White papers, not to exceed 8 pages, must provide the following information: 1.A clear statement of the uniqueness of the idea in response to the challenge problem(s) and in the context of the existing state-of-the-art in protein design. If you choose a challenge problem (or problems) other than the ones in this addendum, you must explain why you believe: a) it is equivalent to or exceeds the challenges posed here; b) it is of interest to DoD; and, c) it requires development of new and revolutionary computational and experimental tools whose development requires a concerted effort by an interdisciplinary team of scientists drawn from the fields of chemistry, math, physics and biology. We are looking for ideas that will generate revolutionary capabilities if the proposed work is completed successfully over a 5 year period of performance. While distinct goals that target the challenge problem must be identified, the scope of the idea and approach may extend past the 5 year performance period; 2. A concise statement of the scientific and technical challenges, unique approaches, and potential anticipated technical solutions to the challenges that will be addressed. This statement should demonstrate that the proposer has a clear understanding of the state-of-the-art; 3. Explicit timelines and milestone achievements by which progress toward the goals can be evaluated. These milestones should reflect an initial period of performance of 24 months with subsequent milestones reflecting 12 month periods of performance. Milestones must be associated with demonstrable metrics of performance; 4.A cost estimation for resources required for the proposed timeline. This should include a clear description of the human resources needed as well as funding;5. A management plan that describes how the different disciplines represented on the team will be harnessed to demonstrate a solution to the challenge problem(s); 6. A brief summary of the technical expertise of the proposed principal investigator and other key team members. White Paper Deadline and Submission Information. If white papers are received by 1600 EST, Friday, July 16, 2004, DARPA will provide a recommendation to submit or not to submit full proposals by Friday, August 20, 2004. Preproposals received after July16, 2004 may not be reviewed under this addendum. If the authors of white papers choose not to submit electronically, U.S. mail may be used. White papers will not be accepted by way of facsimile transmissions. To facilitate the submission of white papers, a website http://www.sainc.com/dso0412/ has been set up. For more detailed instructions on submitting white papers, please refer to the instructions for BAA04-12 found at the website http://www.darpa.mil/dso. Format and Content of Full Proposals. Follow the general guidelines for full proposal format and content provided at: http://www.darpa.mil/dso. Additional guidelines specific to this addendum are provided below. Please put the phrase Protein Design Process in the title of the proposal. Notwithstanding the disposition of white papers, DARPA will accept full proposals for this addendum. Each full proposal should, in addition: 1.Elaborate on the specific information requested in the instructions for white papers by providing sufficient technical details so as to permit complete evaluation of the feasibility of the idea; 2. Include at least two specific and quantitative technical achievements to be demonstrated at 24, 48 and 60 months. These achievements should permit the evaluation of progress towards solving the challenge problem(s). Proposals with cost share should clearly identify the specific tasks to be cost shared in the technical proposal and separately break out the corresponding costs in the cost proposal. The number of awards will be dependent on the suitability of proposals received and availability of funds. To receive consideration under this addendum PROPOSALS ARE DUE NO LATER THAN 1600 EST, Friday, September 17, 2004, to the address shown below. Proposals received after that date will be considered under the open BAA but not this addendum. If proposals are not submitted electronically, proposers should submit 6 copies of the proposal and an electronic copy of the proposal on a ZIP disk or CD. Proposal Evaluation. Evaluation of the proposals will be in accordance with BAA04-12. For general administrative questions, please refer to the original CBD announcement, BAA 04-12 of February 2, 2004. GENERAL INFORMATION: In all correspondence, reference BAA04-12, Addendum 5. E-MAIL: BAA04-12@darpa.mil.Technical Points of Contact for Protein Design Processes - Dr. Eric Eisenstadt, DARPA/DSO; Phone (703) 696-2322; Fax: (703) 516-8740; Dr. Carey Schwartz, DARPA/DSO; Phone: (571) 218-4536; Fax: (571) 218-4553. Address for Submission of Unclassified White Papers or Full Proposals: DARPA/DSO, ATTN: BAA04-12, 3701 North Fairfax Drive, Arlington, VA 22203-1714. Web address for White Paper Submission: http://www.sainc.com/dso0412/. Web address for Full Proposal Submission: http://www.sainc.com/dso0412/.
- Record
- SN00579933-W 20040506/040504212856 (fbodaily.com)
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