Pilot Grants to Explore the Use of the American Heart Association Protein Binding Atlas to Discover Novel Protein Interactions

The purpose of this request for proposals (RFP) is to solicit applications for innovative pilot projects aimed at predicting and understanding protein-protein and protein-small molecule interactions involved in key biological processes associated with cardiovascular, kidney, and metabolic diseases, including obesity. The proposed projects are encouraged to utilize the American Heart Association (AHA) Protein Portal.

The AHA Protein Binding Atlas was established through a Cooperative Research and Development Agreement between the AHA and the Lawrence Livermore National Laboratory (LLNL). Its objective is to combine world-class technology and high-impact biology to develop a comprehensive reference atlas of cell-protein targets to accelerate and hone drug discovery. The AHA Protein Binding Atlas leverages the world-class high performance computing power of Lawrence Livermore National Laboratory and machine learning algorithms for protein-molecule binding predictions to refine and accelerate candidate drug selection for clinical development. The Protein Binding Atlas consists of approximately two million small molecules fully simulated against nearly 15,000 proteins to model binding predictions. The Atlas is a static database of in-silico calculations of protein-ligand interactions, as well as supplemental information for proteins and ligands, intended to provide insight into drug-candidate molecules regarding on-target interactions and off-target interactions.

The Protein Portal  includes:

• 12,000 human protein models curated for molecular screening
• A library of 2 million small molecules available for binding calculations; currently contains docking/binding calculations against the entire protein database of approximately 800,000 molecules
• Molecular Docking to enable the identification of novel compounds of therapeutic interest, predicting ligand-target interactions at a molecular level, as well as reverse targeting and adverse reaction
• Binding scores and current binding agents for a target, to understand if and how one target might be better than another - potential for competitive analysis for pipeline decisions
• Interaction calculations with varying degrees of completeness for an initial set of ligands: Federal Drug Administration-approved drugs, clinical trial and pre-clinical drugs, and compounds from the ChEMBL, Marine metabolite, and Foodome datasets
• Safety and Pharmacokinetic Property Predictions: For each molecule, the portal also provides prediction values related to safety and efficacy with models generated
• Protein associated pathways from Reactome, SMPDB (Small Molecule Pathway Database), and UniProt

A successful proposal will integrate the AHA Protein Portal and may focus on computational modeling, proteomics, network biology, and systems biology to deliver predictive insights for therapeutic development in these disease areas.
 
A successful proposal will include one or more of the following:

1. Identify Druggable Targets: Investigate and predict small molecules, peptides, or other entities that bind to key proteins involved in cardiovascular, kidney, and metabolic diseases, including
2. obesity.
3. Identify Opportunities to Repurpose Existing Drugs by evaluating “off-target” protein binding that may represent druggable targets.
4. Predict Off-Target Effects: Utilize computational and experimental approaches to predict potential off-target effects of molecules that interact with proteins involved in disease processes. This will aid in improving the safety and specificity of future drug candidates.
5. Predict Ligand-Protein Binding using a Machine Learning Approach
6. Predict the Impact of Post-Translational Modifications (PTMs): Predict how post-translational modifications, such as phosphorylation, acetylation, glycosylation, and ubiquitination, alter the activity and function of proteins relevant to disease pathways.
7. Analyze Gene Mutations and Their Impact on Protein Binding and Function: Investigate how mutations in genes associated with cardiovascular, kidney, and metabolic diseases, including obesity, may alter protein binding dynamics, protein function, and overall disease progression.

Award Details

Duration: Up to one year of funding from date of funding, contingent upon milestones and timelines being met.
Grant Amount: Each award will total $100,000 (including 10% indirect costs)
Number of Awards: The AHA anticipates awarding up to four grants; the AHA reserves the right to determine the final number of awardees.

Proposals are welcomed from researchers with experience in one or more of the following areas: systems biology, network science, medicinal chemistry, protein chemistry, machine learning, artificial intelligence, and molecular biology. Collaborative proposals involving multidisciplinary teams are encouraged. This pilot grant is open to early-stage investigators as well as established researchers exploring new areas of inquiry related to the outlined objectives. All applicants are encouraged to use the AHA Protein Portal in the application and the research grant.

Before you apply

• Each applicant must be an AHA Professional Member before submitting a pre-proposal or full proposal. Join or renew when preparing an application in ProposalCentral, or by phone at 1-888-242-2453 or 972-349-5803. Membership processing may take 3-5 days; do not wait until the application deadline to renew or join.

• For more information, please register and attend our webinar on Wednesday, February 12, 2025 from 11 am-12 CT. Register here.

• Projects can include collaborators from multiple areas of expertise; however, the project proposal must be submitted by a project lead representing an academic or non-profit organization based in the United States.
  
  
• Preference will be given to applicant organizations that are institutes of higher education, public entities, or nonprofits that are tax exempt under Section 501(c)(3) of the Internal Revenue Code and are not private foundations or Type III supporting organizations. Other types of nonprofit and for-profit organizations are also eligible to apply. The American Heart Association may require additional documentation.
  
  
• Organizations that are currently funded through other American Heart Association funding mechanisms can apply.
  
  
• Organizations can submit multiple proposals.
  
  
• Individuals are encouraged to use the AHA Protein Portal in the application and the research grant.  A grant application without integration of the AHA Protein Portal will be deemed unresponsive.

Applications must be submitted using ProposalCentral, the AHA’s online submission portal. The online application requires you to provide information and to answer questions beyond what is captured in this document. Proposal deadline is May 1, 2025.

A review will take place with a diverse group of experts.

• Research Plan may be up to 6 pages (12-point font, single space, 1-inch margins on all sides)
  
  • Specific Aims (1 page)
  • Research and Methods and Operational plan to achieve the aims including how the AHA Protein Portal will be leveraged (3-4 pages).
  • Expected outcomes and deliverables, potential limitations, a timeline, and project success milestones. (1 – 2 pages)

• Works Cited (4-page limit is not included in 6-page limitation)

• Budget Information including:
  • Salary and fringe benefits of the project lead, mentor, collaborating investigators, and other participating research staff or faculty.
  • Project-related expenses including access to data from a third party, travel, and publication costs in accordance with institutional and American Heart Association policies. Please note that the American Heart Association does not fund the costs of program implementation or operations beyond what is established in an approved budget.
  • Maximum of 10% institutional indirect costs may be claimed on the award.

It is highly encouraged that any data analysis for your project be conducted via the American Heart Association’s Precision Medicine Platform, powered by Amazon Web Services. Our intent is to help applicants gain confidence leveraging cloud computing for applications and projects.

• Although we are highly encouraging the use the Precision Medicine Platform, we are not making it a requirement. We understand that a researcher may have certain restrictions that make it difficult to use the Precision Medicine Platform based on data and/or institution.
• There may be some cases where the data you will be analyzing is only approved for use in an already approved analytic environment/server and you would need to seek additional approval to upload it into a secure workspace on the Precision Medicine Platform.  The timing of getting this approval may or may not work with the start of the award (if awarded), etc.  

The Precision Medicine Platform provides you with a secure cloud computing workspace for you to use for the application and during the term of the award that allows researchers to code in various languages, including R and Python, and to use statistical software including but not limited to SAS and R studio. The most up-to-date machine learning and artificial intelligence software available from Amazon Web Services is also included. Researchers are also able to install their own tools.

The American Heart Association asks that the grantees also accelerate collaboration through the sharing of data and code as well as the coordination for interoperability of data to facilitate findability and sustainability. The American Heart Association fully supports the FAIR (Findable, Accessible, Interoperable and Reusable) guiding principles of data stewardship.  The Precision Medicine Platform helps to support this principle by also serving as a data marketplace and enables you to share your data and make it available to other researchers. If you were to make your data available on the Precision Medicine Platform by request at the conclusion of your award, you will be set up in our system to receive electronic notifications of these requests that you will review and approve.

Learn more about the AHA Precision Medicine Platform:

• Getting Started
• Uses
  
• Tools & Features
• Security Information

Additional Requirements

• The projects submitted can have no scientific or budgetary overlap with other work funded by the AHA or any other source.
• Any inventions, intellectual property, and patents resulting from this funding are governed by the AHA’s Patent, Intellectual Property and Technology Transfer Policy.
• The applicant/awardee and institution are responsible for compliance with all AHA research award policies and guidelines for the duration of any awards they may receive.
• Visit the Research Programs Awards Policies page for more information on the above topics: American Heart Association Awardee Resources

Final progress report
Awardees must submit a final progress report. Progress reports may take the form of a required written report in addition to video conferencing, phone calls, and/or face-to-face visits. Reporting will be focused on achievement of stated milestones as indicated in the project timeline. The American Heart Association reserves the right to request additional updates, site visits, or reporting.

Public access
The American Heart Association’s public access policy requires that all journal articles resulting from American Heart Association funding be made freely available in PubMed Central and attributed to a specific American Heart Association award within 12 months of publication. It is the responsibility of the awardee to ensure journal articles are deposited into PubMed Central