# Investigating structure activity relationships in autoprocessing by HIV-1 protease

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $209,375

## Abstract

Project Summary
The long-term goal of this project is a detailed mechanistic understanding of the autoprocessing
mechanism by which viral proteases cut themselves out of precursor polyproteins. Autoprocessing is
critical to the life cycle of many viruses, but is poorly understood in part because the structure of
protease in polyproteins is highly dynamic. In Aim 1, we will determine the potency of a panel of
inhibitors for autoprocessing of HIV-1 protease. The results from this aim will provide a guide to
understand the physical properties at different positions on inhibitors that govern binding. In Aim 2, we
will use deep mutational scanning to determine how all possible point mutations in protease impact
autoprocessing efficiency. The results from this aim will determine the physical requirements at each
position in protease for autoprocessing. Together, these aims will provide a detailed understanding of
the physical underpinnings of autoprocessing by HIV-1 protease.

## Key facts

- **NIH application ID:** 10374940
- **Project number:** 5R21AI157871-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** DANIEL N BOLON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2021-03-19 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374940

## Citation

> US National Institutes of Health, RePORTER application 10374940, Investigating structure activity relationships in autoprocessing by HIV-1 protease (5R21AI157871-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10374940. Licensed CC0.

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