# TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular Neighborhoods

> **NIH NIH P41** · ROCKEFELLER UNIVERSITY · 2021 · $174,356

## Abstract

PROJECT SUMMARY
TR&D Project 4. The Modeling Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems
in Cellular Neighborhoods
Here, we are concerned with the modeling of (i) static structures of large macromolecular machines and (ii)
dynamic processes involving these machines. The accuracy, precision, and completeness of these models can
in principle be improved by using all available information (ie, integrative modeling), including from various
experiments, physical theories, statistical analyses, and prior models. We will improve several aspects of
integrative modeling, tuning these improvements to the biological systems and data described in TR&Ds, DBPs,
and C&SPs, and then implementing them in our open-source Integrative Modeling Platform (IMP) package. To
improve integrative modeling of structures of macromolecular complexes, we will: (i) develop integrative
modeling relying on near-atomic resolution cryo-electron microscopy density maps; (ii) develop explicit atomic-
resolution representation of chemical cross-links; (iii) develop a scoring function for integrative modeling of
related complexes from multiple species; and (iv) develop a sensitive Bayesian scoring function for assessing a
model against cryo-EM single particle images. To improve integrative modeling of dynamics of macromolecular
systems, we will: (i) estimate kinetic rate constants for changes in structure and composition based on time-
dependent cryo-EM images; and (ii) develop integrative modeling of long macromolecular processes by
satisfaction of spatiotemporal data. Finally, we will also leverage our method development efforts by supporting
other developers and users of IMP.

## Key facts

- **NIH application ID:** 10140371
- **Project number:** 5P41GM109824-08
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** ANDREJ SALI
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $174,356
- **Award type:** 5
- **Project period:** 2014-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140371

## Citation

> US National Institutes of Health, RePORTER application 10140371, TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular Neighborhoods (5P41GM109824-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10140371. Licensed CC0.

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