[Federal Register Volume 64, Number 88 (Friday, May 7, 1999)]
[Notices]
[Pages 24628-24630]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-11532]


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DEPARTMENT OF ENERGY


Office of Science Financial Assistance Program Notice 99-19; 
Computational Structural Biology

AGENCY: U.S. Department of Energy (DOE).

ACTION: Notice inviting grant applications.

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SUMMARY: The Office of Biological and Environmental Research (OBER) of 
the Office of Science (SC), U.S. Department of Energy (DOE), hereby 
announces its interest in receiving grant applications in its 
Computational Structural Biology subprogram. There is an immediate

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need for greatly improved computational approaches for gene product 
structure and function elucidation. This solicitation seeks 
sophisticated prediction, modeling and simulation research for the 
exploration of the interrelationship of macromolecular sequence, 
structure and function. The goal will be to establish a robust 
computational process for predicting the three-dimensional architecture 
for gene products and for gaining further insight into their biological 
role.

DATES: Before preparing a formal application, potential applicants are 
encouraged to submit a brief preapplication. All preapplications, 
referencing Program Notice 99-19, should be received by DOE by 4:30 
P.M., E.D.T., June 15, 1999. A response discussing the programmatic 
relevance of the proposed submission will be communicated by July 1, 
1999. Formal applications submitted in response to this notice must be 
received by 4:30 P.M., E.D.T., October 5, 1999, to be accepted for 
merit review and consideration for award in mid-Fiscal Year 2000.

ADDRESSES: Preapplications referencing Program Notice 99-19, must be 
sent by E-mail to [email protected]. Preapplications will 
also be accepted if mailed to the following address: Ms. Sharon Betson, 
Office of Biological and Environmental Research, SC-73, 19901 
Germantown Road, Germantown, Maryland 20874-1290.
    Formal applications, referencing Program Notice 99-19, should be 
forwarded to: U.S. Department of Energy, Office of Science, Grants and 
Contracts Division, SC-64, 19901 Germantown Road, Germantown, Maryland 
20874-1290, ATTN: Program Notice 99-19. This address must also be used 
when submitting applications by U.S. Postal Service Express Mail or any 
other commercial overnight delivery service, or hand-carried by the 
applicant. An original and seven copies of the application must be 
submitted.

FOR FURTHER INFORMATION CONTACT: Dr. Charles G. Edmonds, Office of 
Biological and Environmental Research, SC-73, U.S. Department of 
Energy, 19901 Germantown Road, Germantown, MD 20874-1290, telephone: 
(301) 903-0042, FAX: (301) 903-0567, E-mail: 
[email protected]. The full text of Program Notice 99-19 
is available via the Internet using the following web site address: 
http://www.er.doe.gov/production/grants/grants.html.

SUPPLEMENTARY INFORMATION: The Office of Biological and Environmental 
Research supports a directed, basic research program in the areas of 
environmental, life and medical science. Major research program 
emphases are placed on characterization of human and microbial genomes, 
model organisms for understanding human gene function, structural 
biology, the biological effects of low dose radiation, global climate 
change, improved technology for cleanup of DOE contaminated sites, 
advanced imaging technologies, and molecular nuclear medicine. With the 
accelerating increase in nucleic acid and derived amino acid sequence 
data flowing from genome projects and in the particular context of 
these DOE supported basic research efforts, there is an immediate need 
for greatly improved experimental and computational approaches for gene 
product structure and function determination. OBER presently supports a 
program in computational structural biology that is intended to address 
this need.
    This notice is to solicit applications for grants to maintain and 
enhance this program which focuses on sophisticated prediction, 
modeling and simulation research to provide a generalizable approach to 
the interrelationship of macromolecular sequence, structure and 
function. The rapid influx of newly discovered genes, the remarkably 
large proportion of which no function can so far be inferred, require a 
global predictive capability. We are seeking tools for the robust 
prediction of structure and inference of function for any gene and on a 
whole genome scale of analysis.
    Research applications that integrate existing software tools in 
novel ways and/or develop new computational strategies to exploit 
databases of macromolecular structural information, including both high 
and low resolution structures, are a continuing interest of the 
program. This includes the goals of predicting the structure and 
function of newly discovered gene sequences as well as the prediction 
or computational design of the chemical properties and architectural 
arrangement of proteins or nucleic acids needed for a particular 
functional application. Examples of existing approaches that fall into 
this category are knowledge-based or molecular extension methods (e.g., 
homology model building), ab initio structure prediction (finding 
structures that fit sequences) and the development of tools to assign 
existing or new sequences to specific structures (e.g., finding 
sequences that fit structures through threading or inverse folding 
algorithms). Attention may also be focussed on the problem of negative 
design, the identification of aspects of sequence that precludes its 
fitting a known structure. Awardees will be expected to attend the 
biannual Critical Assessment of Techniques for Protein Structure 
Prediction (CASP) experiment and participate at an appropriate level in 
the comparative exercise.
    Further, the use of structure from experimental and/or 
computational sources to provide insight into function is a specific 
target of this solicitation. Computational and visualization techniques 
exploiting structure to characterize recognition within macromolecular 
ensembles, ligand-receptor and other specific molecular interactions 
and to extend this to the understanding and modeling of elaborate 
functional aggregates including metabolic pathways and interacting 
circuits are specifically encouraged. This solicitation includes but is 
not limited to participation in structural genomics projects, i.e., the 
collaborative experimental, theoretical and computational efforts which 
seek to establish a catalogue of the structures of a representative set 
of protein folds occurring in nature and thus facilitating the modeling 
of the structure of any genomically derived amino acid sequence by 
reference to its nearest catalogued archetype.
    Applications that exploit the latest multiple approaches (in 
algorithms, simulation, modeling and graphical representation/
visualization) or provide for the interpretation and the integration 
and joint utilization through the World Wide Web of the growing body of 
sequence, structural and physical information tools will also be 
considered particularly responsive. We encourage the development of 
teams to accelerate the deployment of robust software available to the 
entire community. Established programs should demonstrate such 
capabilities or discuss plans for web access and dissemination. The 
long term goal of the program is to develop well-integrated software 
packages that meet the scientific and technical goals outlined above.
    The transformation of the accumulating database of genomic 
information into a practical understanding of structure-function 
relationships in biological macromolecules and of the complicated 
systems which constitute living cells, tissues and organisms is 
paramount. The ultimate objective of the extension of this new 
understanding of individual reactive entities to the genome scale will 
be the elucidation of a vocabulary and

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grammar of connectedness in molecular function. Through escalating 
levels of complexity from functional aggregates to metabolic circuits 
and homeostatic networks we will arrive at a systems view of biology. 
This will enable diverse applications in human health, including 
individualized medicine and drug design, in biotechnology, including, 
new and improved biomaterials and new biocatalysis in industry and 
manufacturing, in environmental science for the design of enzymes for 
effective and efficient removal of environmental contaminants and in 
energy technology for the development and conversion of biomass for 
fuels.

Program Funding

    It is anticipated that approximately $2.0 million will be available 
for multiple grant awards during Fiscal Year 2000 contingent upon the 
availability of appropriated funds. Applications may request project 
support up to three years, with out-year support contingent on the 
availability of funds, progress of the research, and programmatic 
needs. We expect to award several grants in this area of research of up 
to $500,000 per year.

Preapplications

    A brief preapplication should be submitted. The preapplication 
should identify on the cover sheet the institution, PI name, address, 
telephone, fax and E-mail address for the principal investigator, and 
title of the project. The preapplication should consist of two to three 
pages narrating the research objective, methods for accomplishment and 
benefits of the effort.
    Preapplications will be evaluated relative to the scope and 
research needs for the Computational Structural Biology subprogram.
    Applications will be subjected to scientific merit review (peer 
review) and will be evaluated against the following evaluation criteria 
listed in descending order of importance as codified at 10 CFR 
605.10(d):
    1. Scientific and/or Technical Merit of the Project.
    2. Appropriateness of the Proposed Method or Approach.
    3. Competency of Applicant's Personnel and Adequacy of Proposed 
Resources.
    4. Reasonableness and Appropriateness of the Proposed Budget.
    The evaluation will include program policy factors such as the 
relevance of the proposed research to the terms of the announcement and 
an agency's programmatic needs. Note, external peer reviewers are 
selected with regard to both their scientific expertise and the absence 
of conflict-of-interest issues. Non-federal reviewers may be used, and 
submission of an application constitutes agreement that this is 
acceptable to the investigator(s) and the submitting institution.
    To provide a consistent format for the submission, review and 
solicitation of grant applications submitted under this notice, the 
preparation and submission of grant applications must follow the 
guidelines given in the Application Guide for the Office of Science 
Financial Assistance Program 10 CFR part 605.
    Information about the development, submission of applications, 
eligibility, limitations, evaluation, the selection process, and other 
policies and procedures may be found in 10 CFR part 605, and in the 
Application Guide for the Office of Science Financial Assistance 
Program. Electronic access to the Guide and required forms is made 
available via the World Wide Web at: http://www.er.doe.gov/production/
grants/grants.html. On the SC grant face page, form DOE F 4650.2, in 
block 15, also provide the PI's phone number, fax number and E-mail 
address.
    The Office of Science as part of its grant regulations requires at 
10 CFR 605.11(b) that a recipient receiving a grant and performing 
research involving recombinant DNA molecules and/or organisms and 
viruses containing recombinant DNA molecules shall comply with NIH 
``Guidelines for Research Involving Recombinant DNA Molecules'', which 
is available via the world wide web at: http://www.niehs.nih.gov/odhsb/
biosafe/nih/rdna-apr98.pdf, (59 FR 34496, July 5, 1994), or such later 
revision of those guidelines as may be published in the Federal 
Register.

    The Catalog of Federal Domestic Assistance Number for this 
program is 81.049, and the solicitation control number is ERFAP 10 
CFR Part 605.

    Issued in Washington, D.C. on April 29, 1999.
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 99-11532 Filed 5-6-99; 8:45 am]
BILLING CODE 6450-01-P