# SEQUENCE DETERMINANTS OF PROTEIN STRUCTURE & STABILITY

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 1990 · $234,429

## Abstract

The long term objective of this research is to understand the
relationship between the amino acid sequence of a protein and the
ability of the protein to fold into a stable, three dimensional
structure.  This is important because an understanding of protein
stability and folding underlies any detailed understanding of most
biological reactions.  Moreover, much of the promise of
biotechnology for improving human health depends on our
eventual ability to manipulate the function of a protein by
altering its sequence.  The studies described here will probe the
determinants of protein folding and stability for three repressor
proteins:  the lambda Cro protein, the N-terminal domain of
lambda repressor, and the P22 Arc protein.  These proteins
provide excellent model systems because their structures are
known or will be known soon, the systems are easily manipulated
genetically, and biochemical and biophysical studies of the mutant
proteins are straightforward.

Our studies will employ classical or modern mutagenesis methods
to create populations of singly or multiply mutant proteins, from
which we will screen or select for proteins with interesting
structural phenotypes.  For example, techniques of reversion
analysis and immuno-screening will be applied to obtain proteins
with enhanced stabilities, and combinatorial cassette mutagenesis
and genetic selection will be used to identify libraries of
sequences that can form beta-turns, mediate symmetric
helix/helix packing, or allow highly efficient nucleation of alpha-
helix formation.  Equilibrium constants for denaturation and
dimerization of the mutant proteins will be determined, and in
some cases peptide synthesis or site-directed mutagenesis will be
used to test specific hypothesis concerning the molecular
mechanisms of the observed changes in structure or stability.  The
structures of interesting mutant proteins will be investigated by
collaborative crystallographic or nuclear magnetic resonance
experiments.

## Key facts

- **NIH application ID:** 3126364
- **Project number:** 5R01AI015706-12
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **SAM.gov UEI:** E2NYLCDML6V1
- **Principal Investigator:** Robert T Sauer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $234,429
- **Award type:** 5
- **Project period:** 1979-05-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126364

## Citation

> US National Institutes of Health, RePORTER application 3126364, SEQUENCE DETERMINANTS OF PROTEIN STRUCTURE & STABILITY (5R01AI015706-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126364. Licensed CC0.

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