# Protein Interfaces and Aggregation

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $319,314

## Abstract

ABSTRACT
Nonenveloped organelles govern many cellular functions including aspects of signaling. These cellular bodies
are made up of proteins and nucleic acids which have condensed, or phase separated out of the components
within the cell. The coupling of structure and miscibility properties of polypeptides and nucleotides underly the
formation of non-enveloped organelles or biomolecular condensates. We propose theoretical and computational
methods to quantify the contributions of number of protein components, structural/conformational disorder and
phosphorylation to biomolecular condensate formation. Each of the polypeptide components interact and form
an interface with other molecules in the biomolecular condensate. These interactions drive the formation of these
cellular structures. This is not a protein or peptide interface prediction project, but rather we seek to understand
the interactions and entropic components of the underlying free energy surface driving the creation of the
solubility limit and the consequent phase transition forming the condensates. We propose to calculate the
properties of polypeptide biomolecular condensates by simulating and analyzing the liquid-liquid phase
separation at the all-atom model level. We will explicitly consider the role of peptide disorder, the number of
components and their chemical characteristics that allow condensation out of the cytosolic mixture. Deciphering
the thermodynamic manifold, entropic versus enthalpic driving forces as well as compositional dependences is
necessary to understand the formation and stability of these cellular physiological assemblies. Once condensed
the kinetics of the system is governed in part by the diffusion of the components both within the condensate and
in its formation or dissolution. The rate constants for polypeptide transport will be explicitly calculated to consider
the effects of sequestration given the properties of the sequence. Differentiation of physiological versus
pathological assemblies and, as such, plausible therapeutic solutions targeting these structures will not be
possible without these fundamental mechanistic insights.

## Key facts

- **NIH application ID:** 10155494
- **Project number:** 5R01GM037657-29
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Bernard MONTGOMERY PETTITT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,314
- **Award type:** 5
- **Project period:** 1988-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155494

## Citation

> US National Institutes of Health, RePORTER application 10155494, Protein Interfaces and Aggregation (5R01GM037657-29). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155494. Licensed CC0.

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