HIGH-ACCURACY PROTEIN STRUCTURE MODELING

RELEASE DATE:  July 8, 2004
 
RFA Number:  RFA-GM-05-008  

EXPIRATION DATE:  February 15, 2005

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. Replacement R01 (RFA-GM-07-003) 
funding opportunity announcement has been issued for the 
submission date of June 1, 2006 and submission dates thereafter.

Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATION:  
National Institutes of Health (NIH)
 (http://www.nih.gov/)

COMPONENT OF PARTICIPATING ORGANIZATION:   
National Institute of General Medical Sciences (NIGMS)
 (http://www.nigms.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:  93.859(NIGMS)
 
LETTER OF INTENT RECEIPT DATE:  January 14, 2005
APPLICATION RECEIPT DATE:  February 14, 2005  
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The NIGMS invites applications for P20 Exploratory Center Grants to 
support the development of novel technologies that will significantly 
improve the accuracy of comparative modeling methods for protein 
structure prediction.  This program is part of the NIGMS-supported 
Protein Structure Initiative (PSI).  The purpose of this RFA is to 
foster rapid advances in high-accuracy protein structure modeling by 
promoting interdisciplinary collaborative research with the aim of 
producing models comparable in quality to experimentally determined 
structures for most proteins.  
  
RESEARCH OBJECTIVES

Background

With the completion of well over a hundred genome sequences including 
the human genome, functional characterizations of proteins encoded by 
the genomes have inevitably come to the front of the stage.  Three-
dimensional (3D) structural studies provide a unique contribution in 
understanding the functions of proteins, and enabling structure-based 
drug design.  Recent technology advances in X-ray crystallography and 
NMR spectroscopy have dramatically reduced the time and effort required 
for protein structure determination, making it possible to consider a 
strategy of high-throughput structure determination for a large number 
of proteins composing functional related families, signaling pathways, 
and entire proteomes.  

The NIGMS launched the PSI program in 2000 to explore different 
approaches to large-scale protein structure determination (see program 
information at http://www.nigms.nih.gov/psi/).  The long-range goal of 
the PSI is to make 3D structures of most proteins easily obtainable 
from knowledge of their corresponding DNA sequences.  The PSI program 
is projected to determine about 8,000 experimental structures of 
protein family representatives by 2010.  With improved methods of 
comparative modeling, it may be feasible to produce a million high-
resolution protein structure from the 8,000 that will be directly 
determined experimentally.  The efficiency in experimental structure 
determination and the quality of the computational models will be the 
two main determinants of the overall success of the PSI program.  

The PSI research centers are making rapid progress on the experimental 
front.  The number of structures determined by these centers has 
doubled every year, while the average cost per structure is continually 
dropping.  Unlike most of the submissions to the Protein Data Bank 
(PDB) that are highly homologous to previously determined structures, 
the majority of the structures solved by the PSI centers have 30% or 
lower sequence identity to previous depositions in the PDB.  Since 
these PSI structures have much lower redundancy to known structures, 
they will provide much broader coverage of sequence families and 
possible protein folds.  The production phase of the PSI is scheduled 
to start in the summer of 2005 (see RFAs at 
http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-05-001.html and 
http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-05-002.html).  It 
is anticipated that in two to three years, the number of non-redundant 
structures produced by these large-scale structural genomics centers 
and other structural biology laboratories will be over one thousand a 
year.  The availability of these structures will enable homology 
modeling for several hundred thousand proteins.  The value of these 
structural models in biological research depends critically on their 
quality.  Development of high-accuracy computational methods that 
reliably generate experimental-quality structural models will be 
essential for capitalizing on the PSI investment, and furthermore will 
benefit all biomedical researchers relying on structural information of 
proteins for their functional investigations.  

Unlike the rapid advances made in experimental structure determination, 
progress in computational structure prediction has been incremental as 
illustrated at the recent CASP (Critical Assessment of Methods for 
Structure Prediction of Proteins, http://www.forcasp.org) competitions.  
Predictions that rely on closely related template proteins with known 
structures in general have much higher quality than ab initio methods.  
Reliability of these “homology modeling” or “comparative modeling” 
methods depends critically on the level of sequence identity between 
the modeling target and the template.  When sequence identity is 30% or 
higher, backbone atoms are usually correctly modeled.  The majority of 
the errors come from side-chain and loop placement during refinement 
with roughly 3-4 angstrom root mean square deviation (RMSD) compared to 
high-resolution crystal structures.  When the sequence identity drops 
below 30%, misalignment happens frequently and model quality suffers 
dramatically.  To increase the utilization and value of the 
computational models in biomedical research, and to reduce the need for 
still costly experimental structure determination, significant 
improvement in the reliability and accuracy of modeling techniques is 
needed by the research community.

Recognizing the need for much improved protein structure modeling 
technology, the NIGMS organized a High-Accuracy Comparative Modeling 
Workshop soliciting community input in October, 2003.  The workshop 
participants identified some specific areas as bottlenecks for further 
development of protein structural modeling.  A workshop summary is 
published on the NIGMS website 
(http://www.nigms.nih.gov/psi/reports/comparative_modeling.html).  

The aim of this RFA is to foster scientific progress in computational 
protein structure prediction that will reliably produce models with 
accuracy close to experimentally determined X-ray crystal structures.  
In order to achieve this goal, novel concepts and strategies are needed 
to significantly improve current comparative modeling methods.  Close 
collaborations among creative researchers with various training 
backgrounds and expertise are expected to provide cross fertilization 
for the development of new approaches.  Although hurdles are still 
high, potential payoff and impact will be dramatic.  The ultimate goal 
is a paradigm shift in structural biology, so that experimental 
structure determination for most soluble single proteins will become 
unnecessary, and more resources and effort can be put into 
characterizations of complexes and more difficult targets.  Eventually, 
accurate structural information will be available for all the gene 
products. 

Scope of Research

This RFA aims to promote interdisciplinary team research and 
exploratory approaches in developing novel comparative modeling 
technology.  Cross-disciplinary collaborations with the inclusion of, 
for example, physicists, mathematicians, computer scientists, and 
statisticians who are new to the field are required.  Collaborations 
with the PSI research centers 
(http://www.nigms.nih.gov/psi/centers.html) are encouraged.  The 
technologies developed should be scalable for applications on larger 
data sets of various kinds of proteins, rather than on a limited number 
of a special kind of proteins.  

Applicants for this RFA should focus on one or both of the following 
two main goals (also see Award Criteria):

1) Comparative Modeling Goal 1:  Crystal Structure Quality for Close 
Homologs of Known Structures

The first scientific goal of this RFA is to achieve the standard of 
high-resolution X-ray crystal structure quality for comparative models 
that are based on known structures with higher homology (30% sequence 
identity) to the modeling targets.  This is predominantly a high-
accuracy refinement problem, although substantial improvement of 
alignment methods is also required.  The aim is to acquire the ability 
to reliably produce computational models with highly accurate placement 
of both backbone and side chain atoms, and to significantly reduce the 
need for experimental structure determinations for close homologs of 
known structures. 

2) Comparative Modeling Goal 2:  High-Accuracy Models for Remote 
Homologs of Known Structures

The second scientific goal is to expand the modeling coverage to more 
distantly related proteins that exhibit as low as 10% identity to any 
known structures.  The quality of these models should be close to X-ray 
structures or high-resolution NMR structures with less than 2 angstrom 
RMSD for backbone and side-chain atoms.  This is both an alignment 
problem and a refinement problem.  Significant improvement of modeling 
methods is needed to push the modeling coverage to remote homologs of 
existing structures without much compromise on quality.

Through this RFA, the NIGMS is committed to achieving both of these two 
goals (see Award Criteria).  Applicants must identify which of the 
modeling goals (or both) the proposal is addressing.  Applicants may 
propose intermediate goals and deliverable milestones within the 
funding period.  Although not the main focus, some other kinds of 
studies can be incorporated as components of their research.  These may 
include: establishing benchmarks and standards for quality assessment 
and uncertainty estimations of the models; developing methods that will 
accurately predict structural changes caused by small mutations; 
combining computational methods and high-throughput experimental 
methods to develop novel hybrid approaches; improving ab initio methods 
for loop modeling; designing robust software packages that will build 
models for a large number of proteins with high accuracy and little 
human intervention; collaborating with other scientists to promote 
utilization of the models in functional studies.  Applicants may also 
propose other research, but all activities must be in support of 
reaching the main goals above.

The NIGMS strongly encourages potential applicants to discuss their 
ideas with Institute program staff and to send a letter of intent prior 
to submission to ensure that the application will be responsive to the 
mission and intent of this RFA.

MECHANISM OF SUPPORT

This RFA will use the NIH P20 Exploratory Center Grant award mechanism.  
As an applicant you will be solely responsible for planning, directing, 
and executing the proposed project.  The earliest expected award date 
is December 2005.  This RFA might be reissued for a second time with a 
submission deadline in early 2006 and an expected award date in late 
2006.  P20 Exploratory Center Grants will not be renewable, but rather 
are expected to lead to mature projects that can attract funding 
through other mechanisms.  

This RFA uses just-in-time concepts.  

FUNDS AVAILABLE
 
The NIGMS intends to commit approximately $3 million total cost in 
FY2006 to fund three to four P20 Exploratory Center Grants in response 
to this RFA.  An applicant may request a project period of up to three 
years and a budget of up to $750,000 total costs per year.  Because the 
nature and scope of the proposed research will vary from application to 
application, it is anticipated that the size and duration of each award 
will also vary.  Although the financial plans for the Institute include 
funds to support this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications.

ELIGIBLE INSTITUTIONS
 
You may submit an application if your domestic institution has any of 
the following characteristics:

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  

Applications from foreign institutions will not be accepted; however, 
researchers from foreign institutions can participate through 
collaboration with domestic applicants or subcontracts.
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.   
 
SPECIAL REQUIREMENTS 

The P20 Exploratory Center Grant mechanism is designed to support 
multi-investigator team pilot research.  It is expected that a cohesive 
group with a minimum participation of three investigators should form 
the body of the research team.  Active participation of at least one 
investigator from the scientific disciplines other than structural 
biology, such as physics, mathematics, computer science, and 
statistics, who brings novel ideas and strategies to the design of the 
center’s research plans, is required.  The level of originality of the 
research design and the level of participation of the investigator who 
has not previously worked on protein structure modeling in the research 
projects will be important review criteria.  Plans should be presented 
in the application to integrate the efforts of the individual 
investigators and make the team a cohesive research center.  
Investigators currently supported to work on protein structural 
modeling are eligible to apply; however, their contributions to the 
center projects must not overlap with or be simple extensions of their 
supported studies.

The NIGMS encourages the applicants to make plans to interact and/or 
collaborate with the PSI research centers that will be funded in the 
production phase or other research centers with similar goals.  Target 
selection for experimental structure determination in the PSI centers 
is an evolving process, which usually involves clustering protein 
sequences into families of fine granularity (30% sequence identity) or 
coarse granularity (psi-blast or other profile based clustering 
algorithms).  Following sequence clustering, representatives from the 
sequence families are selected for experimental structure 
determination.  Examples of collaboration may include modeling proteins 
that are homologs of the structures determined by the PSI centers, 
predicting structures prior to release of their experimental structures 
by the PSI centers for quality assessment of the modeling algorithms, 
or development of hybrid approaches by combining computational methods 
with high-throughput experimental data to increase modeling quality.  
Other forms of collaboration with the PSI centers or other large-scale 
experimental structure determination projects are also encouraged.  
Additional plans to engage the user community and to solicit feedback 
to improve quality and utilization of models should also be included.

Funded P20 center principal investigators (PIs) are required to attend 
and report the progress at the annual PSI meetings of the PSI research 
center PIs, the PSI Advisory Committee members, and the NIH program 
staff.  Applicants should request travel funds in their budgets for the 
PIs to attend this annual meeting.

The NIH requires that all products generated in the centers through 
this program become readily available to the entire research community.  
Applicants should develop and propose specific plans for sharing of 
data, materials, protocols, and resources, taking into consideration 
the guidance issued by the NIH http://ott.od.nih.gov/ and 
http://grants.nih.gov/grants/policy/data_sharing.  

There is no prescribed single license for software produced in this 
project.  However NIH does have goals for software dissemination, and 
reviewers will be instructed to evaluate the dissemination plan 
relative to these goals:

1) The software should be freely available to biomedical researchers 
and educators in the non-profit sector, such as institutions of 
education, research institutes, and government laboratories.  

2) The terms of software availability should permit the 
commercialization of enhanced or customized versions of the software, 
or incorporation of the software or pieces of it into other software 
packages.  

3) The terms of software availability should include the ability of 
researchers outside the center and its collaborating projects to modify 
the source code and to share modifications with other colleagues as 
well as with the center.  The application should include written 
statements from the officials of each of the applicant institutions 
responsible for intellectual property issues, to the effect that the 
institution supports and agrees to abide by the software dissemination 
plans put forth in the proposal.

The plans for data sharing must be approved by NIH staff prior to 
award.
 
WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial or grants 
management issues:

o Direct your questions about scientific/research issues to:

Jerry Li, M.D., Ph.D.
Cell Biology and Biophysics Division 
National Institute of General Medical Sciences
45 Center Drive, Room 2As.19F, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0682
FAX:  (301) 480-2004
Email:  lij@nigms.nih.gov

o Direct your questions about peer review issues to:

Helen R. Sunshine, Ph.D.
Chief, Office of Scientific Review
National Institute of General Medical Sciences
45 Center Drive, Room 3AN.12F, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-2881
Email:  sunshinh@nigms.nih.gov

o Direct your questions about financial or grants management matters 
to:

Ms. Grace Olascoaga
Grants Management
National Institute of General Medical Sciences
45 Center Drive, Room 2An.32E, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5520 
Email:  olascoag@nigms.nih.gov
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC staff to estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document (January 14, 2005).  The letter of intent should be 
sent to:

Jerry Li, M.D., Ph.D.
Cell Biology and Biophysics Division 
National Institute of General Medical Sciences
45 Center Drive, Room 2As.19F, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0682
FAX:  (301) 480-2004
Email:  lij@nigms.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). Applications must 
have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) 
number as the Universal Identifier when applying for Federal grants or 
cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 document is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.
 
SUPPLEMENTARY INSTRUCTIONS: 

Applicants should follow the general instructions for PHS 398 
application form with the exception of specific instructions relevant 
to this RFA given below.

1. Description (Page 2)  

In the Description, applicants should describe concisely the goal of 
the research, the innovative nature of the strategy, tasks for each 
component of the center, and the specific target to be reached at the 
end of the project period.  

2. Research Plan  

The total page limit for items a-d of this section is 20 pages.

o Item a: Specific Aims  
The two main goals of this RFA are to increase model qualities to a 
level comparable to high-resolution X-ray crystal structures when known 
structures are available with 30% identity to the modeling targets, and 
to increase model quality to near experimental quality with 2 angstrom 
RMSD when known structures are available with 10% identity to the 
targets.  Specific aims should be built around serving one or both of 
these two main goals.  Since team building is an important aspect for 
the Exploratory Centers, it is anticipated that aim(s) in the initial 
phase (first half year) of the project will be focusing on establishing 
a cohesive environment and platform for the proposed team research.  
The Specific Aims may be intermediate steps to a longer-term goal, but 
they should be well defined and achievable in the project period.  

o Item b: Background and Significance  
The applicants are expected to elaborate on the current state of the 
art, technical bottlenecks, innovative nature of the proposed research, 
and its capabilities and potential impact on biomedical research.  A 
compelling reason for conducting the proposed research should be the 
focus of this section. 

o Item c: Preliminary Studies/Progress Report  
The purpose of this RFA is to promote development of novel ideas and 
approaches through close collaboration among researchers with different 
research backgrounds.  It is anticipated that applicants may not have 
extensive preliminary data.  New ideas relevant to this RFA may not 
have been fully tested.  Therefore, applicants should put more emphasis 
on elaborating the rationale, which may be based on published data from 
other laboratories, for the proposed studies.  Preliminary data are not 
required, should be kept to a minimum (within two pages), and will not 
be a major criterion for review.  Applicants should also discuss the 
rationale for assembling the research team, including qualifications 
and selection criteria for the participating investigators and 
collaborators.  

o Item d: Research Design and Methods  
This section should carefully explain how the specific aims will be 
accomplished.  What is the unique contribution of each component?  Why 
is a multi-disciplinary team required for carrying out the proposed 
research?  How will the interdependent collaboration be effective in 
carrying out the research?  What are the plans for collaboration with 
the PSI centers or other large-scale structural biology centers?  If 
there are doubts about the outcomes for early stages of the work, what 
is the contingency plan?  What are the milestones and clear 
deliverables in this grant period?  What is the long-term goal and plan 
for this work?  What are the plans for dissemination of results and 
software developed to the research and user communities?    
 
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and three signed, 
photocopies, in one package to:
 
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and 
all copies of the appendix material must be sent to:

Helen R. Sunshine, Ph.D.
Chief, Office of Scientific Review
National Institute of General Medical Sciences
45 Center Drive, Room 3AN.12F, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-2881
Email:  sunshinh@nigms.nih.gov
 
APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.
 
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes from the previous unfunded 
version of the application.  

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by NIGMS program staff. Incomplete applications will 
not be reviewed.  If the application is not responsive to the RFA, the 
application will be returned without review. 

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIGMS in accordance with the review 
criteria stated below.  

As part of the initial merit review, all applications will:

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications 
under review, will be discussed and assigned a priority score.  
o Receive written critiques.  
o Receive a second level review by the National Advisory General 
Medical Sciences Council.  

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to evaluate the 
application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. The 
scientific review group will address and consider each of the following 
criteria in assigning the application’s overall score, weighting them 
as appropriate for each application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
SIGNIFICANCE: Does this study address the main goals of this RFA as 
specified in the Research Objectives section? If the aims of the 
application are achieved, how will comparative modeling of protein 
structures be advanced? What will be the benefit to other researchers 
and to the biomedical research field in general if the proposed studies 
are supported?

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the project? Does the applicant acknowledge potential problem areas and 
consider alternative tactics? Are the proposed milestones and goals 
feasible and deliverable as planned?  Are the data and software 
dissemination plans adequate and consistent with the requirements in 
the Special Requirements section of this RFA?

INNOVATION: Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative? Does the project 
challenge existing paradigms or develop new methodologies or 
technologies?  This criterion is especially important since this RFA 
aims to promote innovative technology development to substantially 
improve the quality of protein structural modeling. 

INVESTIGATOR: Are the investigators appropriately trained and well 
suited to carry out this work? Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers?  
What are the track records of innovation of the investigators? What is 
the impact of the investigator’s achievement to his/her research field?  
Is there an inclusion of at least one investigator in the research team 
who has not previously worked on protein structure modeling as his/her 
research focus?  Is the investigator who is new to protein structural 
modeling contributing in a significant way to the studies proposed? 

ENVIRONMENT: Does the scientific environment in which the work will be 
done contribute to the probability of success? Do the proposed studies 
take advantage of unique features of the scientific environment or 
employ useful collaborative arrangements? Is there evidence of 
institutional support?  

ADDITIONAL REVIEW CONSIDERATIONS: In addition to the above criteria, 
the following items will be considered in the determination of 
scientific merit and the priority score:

Multi-disciplinary Team:  One purpose of this RFA is to promote 
collaborations between investigators with different training and 
expertise in order to foster development of creative new ideas and 
strategies in protein structure prediction.  Participation of 
theoreticians in the center who were not principally working on protein 
structure modeling in the past is required.  Review of the applications 
will put emphasis on evaluating the logic and sufficiency of 
contributions from each component, as well as the cohesiveness of the 
research team.

Lack of Preliminary Data:  Because of the exploratory nature of the P20 
mechanism, preliminary data are not required and need not be of concern 
to the applicants or the reviewers.  Evaluation will be based on the 
rationale of the proposed research, the originality and potential 
impact, the track records of the investigators on successfully 
developing innovative technologies and methodologies, and the proposed 
milestones and timelines for the research.  Preliminary data are 
allowed in the application, but should be kept a minimum (within two 
pages) and will not be used as a major evaluation criterion. 

BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  January 14, 2005
Application Receipt Date:  February 14, 2005
Peer Review Date:  July, 2005
Council Review:  September, 2005
Earliest Anticipated Start Date:  December 1, 2005

AWARD CRITERIA

Criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities
 
Responsiveness to this RFA will be the major consideration for 
programmatic priorities.  Applicants should focus on one or both of the 
two modeling goals listed under Scope of Research in the Research 
Objectives section of this RFA.  The NIGMS is committed to achieving 
both modeling goals.  The staff will consider total coverage of the two 
goals in the program in making award decisions.  In addition, there 
should be sufficient innovation in the proposal.  The proposed studies 
should be highly collaborative in nature.  Any application that is 
dominated by a single investigator working on insignificant improvement 
of technologies currently supported by the NIH will be considered non-
responsive to this RFA.  
 
REQUIRED FEDERAL CITATIONS 

SHARING RESEARCH DATA:  Investigators submitting an NIH application 
seeking $500,000 or more in direct costs in any single year are 
expected to include a plan for data sharing or state why this is not 
possible. http://grants.nih.gov/grants/policy/data_sharing  
Investigators should seek guidance from their institutions, on issues 
related to institutional policies, local IRB rules, as well as local, 
state and Federal laws and regulations, including the Privacy Rule. 
Reviewers will consider the data sharing plan but will not factor the 
plan into the determination of the scientific merit or the priority 
score.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, 
Internet addresses (URLs) should not be used to provide information 
necessary to the review because reviewers are under no obligation to 
view the Internet sites.   Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet 
site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject 
to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  Awards are made under the 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92.  All awards are subject to the terms and 
conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be 
found at http://grants.nih.gov/grants/policy/policy.htm 

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.

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NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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