# Theory of Biomolecular Diffusion

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $385,760

## Abstract

PROJECT SUMMARY
Molecular diffusion, often steered and accelerated by solute interactions, critically influences the
outcomes of many biological processes. Diffusion is known to influence or control the kinetics of
many enzymes, and the rates of action of such enzymes may be increased by several orders of
magnitude by electrostatic attraction of charged substrates toward the enzyme active sites. Likewise,
electrostatically steered diffusion greatly speeds the interaction of proteins with other proteins, with
nucleic acids, and with macromolecular assemblages on membranes in a variety of processes
essential for cytoskeletal remodeling, cargo transport, gene expression, and signal transduction.
The broad objectives of the proposed work are to provide new computer simulation tools that will
enable the detailed analysis of the role of molecular diffusion in biological processes at the subcellular
and cellular levels, and the application of these tools to selected problems where close contact with
experimental work is possible.
Development will continue on a novel approach to the treatment of hydrodynamic interactions in order
to better describe the significant effects of these interactions in biomolecular associations. A unique,
unified polar-apolar implicit solvation theory invented and developed in past and current grant cycles
(the Variational Implicit Solvent Method) will be extended in a number of important directions to
provide unprecedented accuracy and speed in future Brownian dynamics simulations. Development
will continue on a unique approach for coupling Brownian dynamics simulations for a proper
stochastic treatment in critical domains with efficient continuum treatments elsewhere. We will
develop a method of adding flexible motion to large molecules in Brownian dynamics by making use
of well-developed Markov State models of biomolecular conformational changes. These innovations
will be implemented in our Brownian dynamics simulation package “Browndye”, and will be used to
study a variety of biological systems.
The health relatedness of this work lies in the potential of diffusional simulations to reveal the detailed
dynamics of molecular interactions within healthy cells and how these dynamics may be altered in
pathological situations. This will provide a basis for future work in structure-based drug discovery, in
which small molecules are used to modulate the dynamic processes within the cell.

## Key facts

- **NIH application ID:** 10440358
- **Project number:** 5R01GM031749-41
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Gary Alexander Huber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $385,760
- **Award type:** 5
- **Project period:** 1983-06-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440358

## Citation

> US National Institutes of Health, RePORTER application 10440358, Theory of Biomolecular Diffusion (5R01GM031749-41). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440358. Licensed CC0.

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