# Integrative Modeling of HIV-Human Protein Complexes

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $176,688

## Abstract

The overall goal of the Integrative Modeling Core is to facilitate the analysis and interpretation of multiple
datatypes to identify and characterize the cellular proteins and networks that influence HIV virus replication.
Interfacing with Projects 1-7, this core will employ existing bioinformatics and systems biology approaches, as
well as develop approaches to facilitate unifying mechanistic and structural details with network biology. There
will be a heavy emphasis on the analysis and integration of data derived from proteomic approaches, including
protein-protein interaction (PPI) data derived from the AP-MS and APEX methods; global post-translational
modification (PTM) data (phosphorylation, ubiquitination and acetylation) about host proteins from HIV-infected
primary cells or cell lines, or after introduction of specific HIV proteins; and global protein abundance data after
infection with WT or mutant versions of HIV (Core 1). These datasets will be analyzed separately (Aim 1) as
well as jointly with other datatypes, followed by visualization to gain a deeper understanding of the functional
pathways that are modulated during HIV infection (Aim 2). Finally, in Aim 3, we will determine structures of
HIV-human protein complexes by an integrative approach based on various structural, biochemical, genetic
and proteomic data generated by Cores 1, 3 and 6 for Projects 1, 3, 4, 5 and 6, using the open-source
Integrative Modeling Platform (IMP) package developed in the Sali lab. We will initially focus on Vif-associated
protein complexes using data from XL-MS (Core 1), cryo-EM (Core 3), small-angle x-ray scattering (SAXS),
and X-ray crystallography (Core 6). Initial studies will focus on mapping interaction interfaces between Vif-
CRL5 and APOBEC3 substrates (Project 1), but we will also apply the integrative structure determination
pipeline to other HIV protein complexes, involving Vpu, Nef, Tat, and Rev proteins (Projects 3-6).

## Key facts

- **NIH application ID:** 10229565
- **Project number:** 5P50AI150476-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** ANDREJ SALI
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $176,688
- **Award type:** 5
- **Project period:** 2007-08-27 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229565

## Citation

> US National Institutes of Health, RePORTER application 10229565, Integrative Modeling of HIV-Human Protein Complexes (5P50AI150476-15). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10229565. Licensed CC0.

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