# Development of a Next-Generation Nucleic Acid Force Field

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $290,481

## Abstract

PROJECT SUMMARY/ABSTRACT
Biomolecular simulation is a critical tool for analysis of biopolymer structure and dynamics,
investigation of intermolecular interactions, and design of new ligands and drugs. Simulation, in
turn, is absolutely dependent on accurate and efficient models of the underlying structural
chemistry and energetics in terms of empirical energy functions (“force fields”). Force field
technology is currently in the midst of a generational transition from traditional atom-based point
charges towards more intricate and accurate potentials using better electrostatic models. This
proposal will continue development of the AMOEBA (Atomic Multipole Optimized Energetics for
Biomolecular Applications) force field for nucleic acids (NAs), and extend the coverage of the
model to naturally and synthetically modified NA components. Coupled with our 2013 AMOEBA
protein parameters, the new NA force field will provide a unified model for the most important
biomolecular systems. Current NA force fields lag well behind their protein counterparts in their
ability to accurately model even the most typical structures under physiological conditions. The
next-generation AMOEBA NA force field promises to significantly improve the fidelity and range
of nucleic acids modeling.
Nucleic acids are the major information carrying molecules of life. Under this research project,
we will investigate several key aspects of nucleic acids, and refine the AMOEBA force field. The
structures and functions of NAs are highly dependent upon the salt environment. The interplay
between RNA local structural dynamics and global/tertiary folding is an intriguing question being
addressed experimentally. The ability to model binding energetics, and design small molecule
drugs and synthetically modified oligonucleotides will be an important growth area for future
medical advances. These studies will be carried out in close collaborations with experimental
colleagues. Development of an accurate and transferable next-generation force field will open
up new paths toward understand and prediction of the behavior of natural and designed nucleic
acid molecules.
Finally, adequate sampling of large structures over longer time scales is crucial for future
molecular simulations. The proposed development of high-performance, open source, parallel
computer software will enable widespread application of the AMOEBA force field to nucleic
acids and related biomolecular systems.

## Key facts

- **NIH application ID:** 10000923
- **Project number:** 5R01GM106137-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JAY PONDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $290,481
- **Award type:** 5
- **Project period:** 2013-04-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000923

## Citation

> US National Institutes of Health, RePORTER application 10000923, Development of a Next-Generation Nucleic Acid Force Field (5R01GM106137-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10000923. Licensed CC0.

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