Drug Design Data Resource: A Community Participation Project

If you develop or use software for structure-based drug design or generate data on drug target structures and ligand affinities, you may be interested in the Drug Design Data Resource (D3R) Exit icon. This is an NIGMS-funded project to collect and share high-quality protein-ligand data sets, develop computer-aided drug design workflows, and engage the community through blind prediction challenges.

The D3R, hosted by the University of California, San Diego, continues a program initiated by NIGMS under the Community Structure-Activity Resource (CSAR) Exit icon at the University of Michigan. A goal of this program has been to gather previously unpublished data from the pharmaceutical industry and other sources and to make it available for validating and improving software for predicting ligand poses and interaction energies. Several data sets have already been donated by companies, including Genentech, AbbVie, GlaxoSmithKline, and Vertex, as well as by academic groups. Both resources have also generated data sets internally or in collaboration with academia.

The data sets, which contain X-ray crystal structures of protein-ligand complexes and structure/activity data for multiple series of ligands, represent 13 different drug targets, including most recently for HSP90, MAP4K4, and designed steroid and vitamin D binding proteins. D3R has also collected data on host-guest systems and made this data available as part of the SAMPL Exit icon series of challenges for benchmarking software predictions of “simple” small-molecule chemical properties such as solvation free energy, partition coefficients, and binding to hydrophobic cavities.

Building on the success of its 1st Annual D3R Workshop Exit icon, in which the 2015 Grand Challenge Exit icon was discussed and summarized in a report, D3R just announced the 2016 Grand Challenge Exit icon. It is based on structures of the Farnesoid X receptor (FXR) and runs through February 2, 2017.

The resource also has developed a Continuous Evaluation of Ligand Pose Prediction Exit icon (CELPP) series of tests in collaboration with the World Wide Protein Databank Exit icon (wwPDB) and the Research Collaboratory for Structural Bioinformatics Exit icon (RCSB), another resource supported by NIGMS. The CELPP tests, which are distinct from the Grand Challenge, will provide chemical compound identifiers of bound small molecules in addition to the protein polymer sequence five days before release of 3D coordinates, giving developers an opportunity to predict docked poses each week.

D3R and its predecessor CSAR were developed to meet the needs of the drug design community identified during workshops several years ago. Continued community input and participation, including additional data donations, are important to help D3R fulfill its mission. Data releases can be coordinated with publication in other formats and venues. Contact D3R principal investigators Rommie Amaro and/or Michael Gilson or send email to drugdesigndata@gmail.com to see how you can be involved.

Early Notice: Revised Biomedical Technology Research Resources Program

BTRR September 2016 Advisory Council Presentation

My BTRR presentation at the September 2016 Advisory Council meeting begins at 2:23:15.

At its September 2016 meeting, our Advisory Council endorsed a concept for funding the Biomedical Technology Research Resources (BTRR) program. The concept includes a number of changes that reflect feedback from an expert panel of scientists convened by NIGMS to evaluate the program. In its report, the panel made important recommendations to:

  • Increase the flexibility and nimbleness of the program.
  • Incorporate a broader range of technologies into the program.
  • Increase new research directions and program turnover and implement a comparative review process.
  • Enable better integration of the program with the overall technology development plans at NIGMS.

The revised BTRR program will provide greater flexibility for the investigators to support a wider range of approaches for technology innovation and dissemination. The program will include collaborative subprojects to integrate emerging technologies in fast moving fields and to provide access and dissemination of these technologies. In addition, research resources funded through this program will have greater flexibility to tailor approaches for providing access, training users and disseminating the specific technologies to the communities being served.

These changes will better support the dual mission of the BTRR program: to develop high-impact technologies that enable biomedical research, and to move those technologies into wide use in the community.

We expect a funding opportunity announcement to be published in the NIH Guide later this year. In order to improve consistency in the review of competing applications, the NIH Center for Scientific Review will convene a special study section. We anticipate that most BTRR centers will not be renewed beyond three cycles (15 years) and we will require investigators involved with this program to formulate a sustainability plan for their research resources.

We welcome your input and feedback. You can email your comments to me or post them here.

New Tool for Building Mentor/Mentee Connections

We’re pleased to announce the launch of MyNRMN Exit icon, a free, web-based platform designed to help biomedical researchers and students across the United States connect professionally. MyNRMN is part of the National Research Mentoring Network Exit icon, which NIGMS manages for the NIH Common Fund’s Diversity Program Consortium.

MyNRMN is designed for scientists at every career level. Faculty in more senior roles and established researchers can sign up as mentors. Early career faculty can serve as mentors or be mentees, depending on their needs. Undergraduates, graduate students and postdocs can elect to be peer mentors or sign up to be mentored. The connections you form through MyNRMN might be as simple as asking a question to scheduling formal mentoring sessions.

Some of MyNRMN’s features include:

  • Browsing other registrants’ profiles to connect with people who have similar interests (as on social media sites).
  • Sharing documents and sending direct messages to your connections.
  • Creating a personalized calendar to schedule mentee/mentor meetings, and electing whether you would like to receive text message reminders.
  • Revising and improving your resume with the CV Builder tool (for mentees).

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Partnering with Professional Societies

Not long ago, Jon Lorsch and I and several other NIGMS staff met with the leadership of one of the professional societies that represents many of our grantees. It was an opportunity to discuss NIGMS’ policies and grant mechanisms, hear about challenges that investigators face, and share ideas about how the biomedical research and training environment can be improved.

Meetings of this kind are not unusual, but they are just one of the ways we interact with the society partners related to NIGMS’ mission and, through them, communicate with their members. Another way is by attending the societies’ scientific meetings, where our staff learn about the latest research in the field, conduct grantsmanship workshops, and answer questions about the funding process.

The professional societies help us disseminate—and receive—information. For instance, they share our notices about funding opportunities and changes in NIH policies as well as respond to our requests for information. Leadership from the professional societies attend the open sessions of our Advisory Council meetings and sometimes speak during the public comment period, enhancing the exchange of information between the Institute and our constituency.

We also collaborate with professional societies on specific activities. Recent examples include meetings convened by FASEB on rigor and reproducibility Exit icon and by ASBMB on research training. With ASCB, we co-organized the Life: Magnified exhibit, which brought biomedical science to a public place.

We greatly value our interactions with the societies and invite suggestions for additional ways we can partner.

The Feedback Loop As a Resource for Your Grad Students and Postdocs

This blog is one way that we reach out to the scientific community with information about research and research training policies, funding opportunities, analyses, resources, meetings and other useful news. It’s also a key way in which we get your input on our activities and plans.

When I looked back at some recent posts, I was struck by how many of them are relevant to the graduate students and postdocs in your labs. For example, the post describing our plans to modernize graduate education is a must-read for graduate students, whose ideas and perspective will further inform our efforts. The post on talking to NIH staff about your application and grant provides essential information for postdocs who will soon be independent investigators.

Please encourage your students and postdocs to subscribe to the Feedback Loop as well as to send us their suggestions for topics to cover in future posts.

Talking to NIH Staff About Your Application and Grant: Who, What, When, Why and How

During the life of your application and grant, you’re likely to interact with a number of NIH staff members. Who’s the right person to contact—and when and for what? Here are some of the answers I shared during a presentation on communicating effectively with NIH at the American Crystallographic Association annual meeting. The audience was primarily grad students, postdocs and junior faculty interested in learning more about the NIH funding process.

Who?

The three main groups involved in the application and award processes—program officers (POs), scientific review officers (SROs) and grants management specialists (GMSs)—have largely non-overlapping responsibilities. POs advise investigators on applying for grants, help them understand their summary statements and provide guidance on managing their awards. They also play a leading role in making funding decisions. Once NIH’s Center for Scientific Review (CSR) assigns applications to the appropriate institute or center and study section, SROs identify, recruit and assign reviewers to applications; run study section meetings; and produce summary statements following the meetings. GMSs manage financial aspects of grant awards and ensure that administrative requirements are met before issuing a notice of award.

How do you identify the right institute or center, study section and program officer for a new application? Some of the more common ways include asking colleagues for advice and looking at the funding sources listed in the acknowledgements section of publications closely related to your project. NIH RePORTER is another good way to find the names of POs and study sections for funded applications. Finally, CSR has information on study sections, and individual institute and center websites, including ours, list contacts by research area. We list other types of contact information on our website, as well.

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Support of Structural Biology and PSI Resources

The 15-year Protein Structure Initiative (PSI) ended on June 30, 2015. In preparation for the termination of the program, an external committee of structural biologists and biomedical researchers identified high-priority areas for NIGMS’ future support of structural biology and the preservation of certain PSI resources. Here are some of their key recommendations and what we’re planning to do in response.

Continue to support synchrotron beamlines for macromolecular crystallography.

Recognizing the importance of synchrotron beamlines in modern structural biology, we intend to continue to support these community resources. Part of this effort includes using a new funding approach to ensure that NIH-supported investigators have reliable access to mature synchrotron-based resources.

Maintain the technologies that make structural investigations possible at the most advanced level; meet the need for modern cryo-electron microscopy resources.

We’ll continue to use existing grant mechanisms to support structural biology research, including
X-ray crystallography, NMR, cryo-EM and integrative or hybrid methods. To facilitate the use of
cryo-EM for structure determination we have started a program to provide support for consortia of
cryo-EM labs to upgrade their facilities
. NIGMS is also developing plans for establishing regional
cryo-EM centers that could provide access to state-of-the-art cryo-EM resources for the broader structural biology community.

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Help Spread the Word About Cell Day

Cell Day 2015On November 5, we’ll host my favorite NIGMS science education event: Cell Day! As in previous years, we hope this free, interactive Web chat geared for middle and high school students will spark interest in cell biology, biochemistry and research careers. Please help us spread the word by letting people in your local schools and communities know about this special event and encouraging them to register. It runs from 10 a.m. to 3 p.m. EST and is open to all.

As the moderator of these Cell Day chats, I’ve fielded a lot of great questions, including “Why are centrioles not found in plant cells?” and “If you cut a cell in half and then turn it upside down will the nucleus, ribosomes, and other parts of the cell fall out?” It’s always amazing to hear what science students are thinking or wondering about. I’m looking forward to seeing what fantastic questions we’ll get this year!

Early Notice: Mature Synchrotron-Based Resources Funding Opportunity Plan

At its September 2015 meeting, our Advisory Council endorsed a concept for funding existing NIGMS-supported synchrotron resources in which the technologies have become mature. This plan will align the funding mechanism used to support the beamlines with the goal of ensuring reliable access to these essential resources for structural biology.

In place of the variety of mechanisms we currently use, we intend to issue a funding opportunity announcement (FOA) called Mature Synchrotron Resources (P30) for 5-year, renewable grants in the range of $1-3 million per year in direct costs. The Institute intends to maintain overall support for mature beamline facilities at the same level it has in the past, but to replace the previous constellation of funding mechanisms with a single, more coherent one.

The focus of the FOA will be on user access, training and support in data collection, processing and analysis. Peer review will assess the resources primarily on their ability to meet the research needs of the user community and on the impact the resources have on their users’ scientific productivity. To ensure that the beamlines maintain their state-of-the-art operations, the FOA will also include support for a limited amount of technology development and implementation.

Since the goal of the effort is to improve the stability of current NIGMS-supported synchrotron structural biology resources for community use, the initial funding opportunity will be open only to synchrotron-based resources already supported by NIGMS.

We welcome your input and feedback on these plans. You can email your comments to me or post them here.

Charles Edmonds, Susan Gregurick, Ward Smith and Mary Ann Wu contributed to this blog post.

Reproducibility Update: New Resources and Expected Changes to the SF424 Application Guide

I previously told you about the development of an NIGMS clearinghouse site where members of the research community will be able to find grantee-produced training materials designed to teach rigorous experimental design and enhance data reproducibility. Since then, NIH has established two new related sites. The first is a Rigor and Reproducibility web portal that provides general information about NIH efforts and offers resources that include guidelines for how research results should be reported and links to publications written by NIH authors on rigor, reproducibility and transparency.

The second site is focused on grants and funding and includes a summary of NIH’s proposal to clarify its instructions to applicants to emphasize expectations that rigorous experimental design and reproducibility of results should be considered during the application and review process. You may have read about the changes in a recent Rock Talk blog post that announced the publication of two new NIH Guide notices: Enhancing Reproducibility through Rigor and Transparency and Consideration of Sex as a Biological Variable in NIH-funded Research. We anticipate that the new instructions will be released in the fall of 2015 and will take effect for all research grant applications submitted on or after January 25, 2016.

As always, if you have questions or concerns, contact your program director. We’re also interested in hearing how your lab validates key biological and chemical reagents, so tell us about your procedures!