NextGen Molecular Workflows
Full campaign name:
NextGen Molecular Workflows: Accelerating Discovery Through Integrated Annotation, Simulation, and Critical Metal-Binding Characterization
Identifying the molecular structures that govern metal binding is essential to advancing critical mineral recovery, biotechnology, and biodesign. Ultrahigh-resolution mass spectrometry provides molecular measurements with exceptional mass accuracy and resolving power. When paired with high-accuracy, high-resolution fragmentation data, these measurements can reveal fragmentation patterns and neutral losses, helping narrow the range of plausible structures. However, confirming newly proposed structures requires chemical validation, including ab initio calculations.
The Environmental Molecular Sciences Laboratory (EMSL) is addressing this challenge by combining the molecular annotation capabilities of CoreMS with the molecular simulation workflows of SIMPLE in an integrated, Super Intelligence (SI)-agent-orchestrated platform. Experimental measurements will constrain the molecular search space, while molecular simulations will help confirm candidate structures and assess their metal-binding properties. A broader pool of candidate structures and analogs is also needed. Autonomous, agentic molecular-network workflows, supported by systematic simulations to predict stable metal-organic motifs, can help generate and evaluate these candidates. Coordinated agents and natural-language interaction will make these coupled workflows more accessible to researchers.
Through this Computing, Analytics, and Modeling community science campaign, EMSL will partner with research community members to apply and validate these workflows for addressing scientific questions in the areas of critical minerals and materials, and biodesign. Participants will help identify priority systems and collaborate with EMSL staff to test the platform against their research needs. Collaboration with EMSL's critical metal-binding characterization community science campaign will connect this effort with complementary experimental datasets and expertise.
The campaign will lay the groundwork for scalable, increasingly autonomous molecular discovery across the EMSL user community. Interoperable experimental and computational results will support future machine learning, predictive modeling, and applications in energy, environmental science, and biosystems design.
By participating in this campaign, participants will:
- Help solve a big science problem
- Drive important outcomes
- Advance their own research
Participation
Who should participate?
Researchers with relevant domain expertise, experience, and overlapping interests with integrated mass spectrometry annotation, molecular simulation, and SI-driven characterization of metal-binding molecules are encouraged to submit a proposal for participation in this campaign.
Required participant background
Expertise
Have experience in high-resolution mass spectrometry, molecular annotation, molecular simulation, metal-binding chemistry, or SI-enabled scientific workflows.
Data and research use cases
Possess high-resolution mass spectrometry data, complementary metal-binding characterization data, or molecular simulation datasets that are approved or authorized for sharing and suitable for applying and assessing integrated workflows.
Collaborative research interests
Be interested in working with EMSL to tailor and test agent-orchestrated CoreMS-SIMPLE workflows for molecular structure identification and metal-binding characterization in critical minerals and materials, or biodesign.
How will participants contribute?
Identify and Prioritize Knowledge Gaps and Needs
Identify barriers to resolving molecular structures and understanding metal-binding behavior from high-resolution mass spectrometry data. Help prioritize scientific questions and molecular systems where integrated annotation and simulation can advance critical minerals and materials, and biodesign research.
Supply Data
Contribute research use cases and relevant datasets authorized for sharing, including high-resolution mass spectrometry measurements, complementary characterization data, or molecular simulation results. These contributions will support the use and validation of coupled CoreMS-SIMPLE workflows for community-selected systems.
Expert Input
Contribute expertise in mass spectrometry, molecular annotation, simulation, metal-binding chemistry, or agentic SI to tailor and rigorously test the integrated workflows. Collaborate with EMSL staff to evaluate candidate structures and computational predictions against experimental evidence and apply the approaches to campaign science questions. Provide feedback on workflow usability, natural-language interaction, and opportunities to improve coordination between annotation and simulation.
About the campaign
EMSL brings together advanced mass spectrometry, molecular annotation, and computational modeling to investigate metal-binding molecules and their roles in biological and environmental systems. Its capabilities include a 21 Tesla Fourier transform ion cyclotron resonance mass spectrometer, a high-resolution Orbitrap, CoreMS-based data processing and annotation, and expertise in ab initio calculations, molecular dynamics, and multiscale modeling. This campaign will build on EMSL's capabilities of CoreMS and SIMPLE in an agent-orchestrated platform. It will also connect with EMSL's critical metal-binding characterization campaign, linking computational workflows with complementary experimental data and expertise.
A central challenge is translating molecular composition into structural and functional understanding. Ultrahigh-resolution mass spectrometry provides measurements with exceptional mass accuracy and resolving power. Combined with molecular formulas, high-resolution fragmentation data can reveal diagnostic fragmentation patterns and neutral losses. These data help narrow the range of possible structures, but a single formula may still represent multiple isomers with distinct reactivities, metal-binding properties, and biological or environmental roles. Expert-led, one-molecule-at-a-time analysis cannot readily keep pace with the scale of modern measurements.
This campaign will address the challenge through a bidirectional workflow: CoreMS will use experimental evidence to constrain the molecular search space, while SIMPLE simulations—including ab initio calculations—will evaluate candidate structures and their metal-binding stability. The simulations will also predict stable metal-organic motifs. These predicted motifs will feed into molecular-network analysis, helping expand and connect candidate structures and analogs. Computational predictions will support the assessment of newly proposed structures alongside appropriate experimental validation.
The campaign invites studies focused on defined target systems or candidate molecules that chelate or sequester metals. It also welcomes research that links these molecules to biological function or investigates their roles in biogeochemical processes involving metal-organic compounds. Systematic simulations will help expand the pool of candidate molecules and analogs by predicting stable metal-organic motifs. Community investigators and EMSL staff will jointly identify priority systems, tailor workflows, and assess their performance against research needs.
Coordinated SI agents will orchestrate the feedback loop, extending CoreMS's natural-language interface with a dedicated SIMPLE agent. Experimentalists will gain a more accessible route to computational analysis, while modelers will have experimentally constrained questions and datasets for evaluating predictions. The resulting interoperable data and workflows will support future machine learning, predictive modeling, and increasingly autonomous discovery in the critical minerals and materials, and biodesign domains.
This campaign supports the stated national research and development priorities for FY 2027 and demonstrates how SI-enabled workflows can accelerate discovery in molecular, biological, and environmental sciences. By integrating experimental evidence, first-principles modeling, and agentic workflows, the effort will advance U.S. Department of Energy Biological and Environmental Research program priorities in critical minerals and materials, and biodesign research.
Campaign timeline
- November 5, 2026: Call for proposals
Open call for proposals launches.
- December 1, 2026: Campaign proposal deadline
Deadline for campaign participants to submit proposals for projects contributing to overall campaign goals.
- December 15, 2026: Initiate work on accepted proposals
Work begins on accepted proposals for projects contributing to overall campaign goals.
- December 2026 – September 2027: Apply NextGen molecular workflows
EMSL's integrated NextGen Molecular Workflows are applied to resolve molecular structures and characterize metal binding, addressing high-priority science questions defined by campaign participants.
- September 2027: Complete campaign
Campaign is finished, code is deployed and validated, and integrated workflows are published for adoption by the EMSL user community.
Campaign methods
DEFINE MOLECULAR CANDIDATES FROM EXPERIMENTAL DATA
Use CoreMS molecular annotation and networking workflows to interpret high-resolution mass spectrometry measurements and define experimentally supported molecular search spaces. Integrate complementary data and results from EMSL's critical metal-binding characterization campaign to guide candidate selection for simulation.
REFINE STRUCTURES WITH FIRST-PRINCIPLES SIMULATION
Apply SIMPLE workflows to evaluate candidate molecular structures using ab initio calculations and metal-stability analyses. Feed computational results back into the annotation workflow to filter chemically plausible structures and connect molecular identification with mechanistic understanding of metal binding.
ORCHESTRATE A CLOSED-LOOP DISCOVERY WORKFLOW
Develop a dedicated SIMPLE agent and coordinate it with the CoreMS agent to manage coupled data processing, molecular networking, simulation, and characterization tasks. Extend CoreMS's existing natural-language interface so researchers can direct integrated workflows in which experimental evidence constrains simulations and computational results refine molecular interpretation.
TAILOR AND VALIDATE COMMUNITY-DRIVEN APPLICATIONS
Pair EMSL staff with community investigators to select priority molecular systems and adapt CoreMS-SIMPLE workflows to their scientific questions. Rigorously test the coupled workflows against relevant experimental and computational evidence, drawing on community expertise and complementary metal-binding characterization to assess performance and scientific utility.
PREPARE INTEROPERABLE DATA FOR PREDICTIVE DISCOVERY
Organize experimental measurements, molecular annotations, and simulation outputs into interoperable datasets suitable for machine learning and advanced computing. Prepare these integrated results to support scalable analysis, predictive modeling, and future automated discovery in critical minerals and materials, and biodesign research.
Solve a big challenge
This campaign will address the challenge of determining which molecular structures in complex mixtures govern metal binding, reactivity, and biological or environmental function. Ultrahigh-resolution mass spectrometry will provide measurements with exceptional mass accuracy and resolving power, while high-resolution fragmentation data can reveal diagnostic fragmentation patterns and neutral losses. Together, these data will help narrow candidate structures, but confirming newly proposed structures requires further validation, including ab initio calculations.
EMSL will couple CoreMS molecular annotation capabilities with SIMPLE molecular simulation workflows in an SI-agent-orchestrated feedback loop. Experimental evidence will constrain the search space, while computational predictions will assess structural plausibility and metal-binding stability. Systematic simulations will also help expand the pool of candidate molecules and analogs by predicting stable metal-organic motifs.
EMSL invites studies targeting molecular compounds that chelate or sequester metals, as well as research linking these compounds to biological function or investigating their roles in biogeochemical processes. Community investigators will contribute priority systems, datasets, and expertise to tailor and rigorously validate the workflows. Together, these efforts will advance scalable, experimentally grounded molecular interpretation and support discovery in the areas of critical minerals and materials, and biodesign.
Expected campaign outcomes
INTEGRATED, AGENT-ORCHESTRATED MOLECULAR WORKFLOWS
Deliver a coupled CoreMS-SIMPLE platform in which experimental evidence constrains molecular candidates and first-principles structural and metal-stability calculations refine their chemical plausibility. Coordinated agents and natural-language interaction will enable researchers to direct complex annotation-simulation workflows more intuitively.
COMMUNITY-VALIDATED SCIENTIFIC APPLICATIONS
Deliver tailored, rigorously tested workflows for community-prioritized molecular systems, demonstrating their utility for structural interpretation and metal-binding characterization. Collaboration among EMSL staff, community investigators, and the critical metal-binding characterization campaign will connect computational predictions with experimental evidence to address needs in critical minerals and materials, and biodesign research.
INTEROPERABLE DATA FOR PREDICTIVE DISCOVERY
Produce integrated experimental and computational datasets linking molecular annotations, candidate structures, and simulation results. These machine-learning-ready resources will support predictive modeling, scalable analysis, and future automated discovery across biological and environmental applications.
PUBLICATIONS AND INSIGHTS FOR THE RESEARCH COMMUNITY
The campaign will produce coauthored and peer-reviewed publications that describe workflows, case studies, and datasets.
Advance your research
- Accelerate your science
- Access advanced technology
- Gain experience and key knowledge
- Coauthor scientific publications
Why "community" science campaigns?
Each community science campaign is intended to bring together researchers with a wide variety of expertise to collaboratively tackle strategically identified challenges that are too big for an individual principal investigator or small research team to address alone.
This collaboration between EMSL and the scientific community will enable efforts to target the molecular identification and metal-binding challenges that matter most, grounding integrated CoreMS-SIMPLE workflows in real-world datasets and research needs. Participants' expertise will be essential to tailoring and rigorously validating the agent-orchestrated feedback loop, turning advanced computational workflows into trusted, accessible tools for discovery in critical minerals and materials, and biodesign research.
Contacts
Campaign leaders (science domain experts)
EMSL User Program Services (logistics)