# Understanding Evolution of Protein Function Through Design

> **NIH NIH R35** · SYRACUSE UNIVERSITY · 2021 · $617,786

## Abstract

The work proposed in Project 1 is based on the observation that one can design short Catalytic AMyloid-
forming Peptides (CAMPs) to catalyze chemical reactions with high efficiency in addition to their own self-
assembly. The goals of the proposed work are: 1. to understand the structural and mechanistic basis for the very
high activity of CAMPs; 2. to achieve improved catalytic efficiency and substrate selectivity in CAMPs; 3. to
create amyloid-organic frameworks, a new class of catalytic materials; 4. to develop complex multifunctional,
light-driven and regulated CAMPs with tunable properties for synthesis of complex products. Development and
characterization of catalytic amyloids will advance several fields of biomedical importance. It will set important
structural and functional reference points for the broad community of scientists interested in the role of amyloids
in protein folding, catalysis and health The structure-activity relationships and structural insights generated in the
proposed work will help us better understand the mechanisms of amyloid toxicity and will improve our knowledge
of the structures adopted by more complex amyloid-forming proteins. In addition to its practical value, this
research program will have a profound impact on our understanding of the fundamental aspects of catalysis.
 Project 2 aims to develop a new NMR-based experimental approach to guide directed evolution to fully
realize its potential in repurposing enzymes for new functions. Specifically we will: 1. gain a thorough
understanding of the limits and the applicability of the method; 2. Independently validate the approach in different
protein scaffolds; 3. use NMR guided directed evolution to create high efficient and selective catalysts for
practically important chemical transformations.
 Project 3. The ability of pathogens to neutralize drugs via a newly developed catalytic activity is one of
the mechanisms of drug resistance. Therefore, a deeper understanding of the factors that determine the ability
of proteins to catalyze new chemical transformations is of paramount importance. We aim to determine the
factors that guide evolution of protein function at a molecular level and use these principles to create catalysts
for chemical transformations not found in nature. We will combine a minimalist computational approach with
sophisticated protein engineering tools to create new protein catalysts for a number of different chemical
transformations including those that require metal cofactors.

## Key facts

- **NIH application ID:** 10167015
- **Project number:** 2R35GM119634-06
- **Recipient organization:** SYRACUSE UNIVERSITY
- **Principal Investigator:** Ivan V Korendovych
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $617,786
- **Award type:** 2
- **Project period:** 2016-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167015

## Citation

> US National Institutes of Health, RePORTER application 10167015, Understanding Evolution of Protein Function Through Design (2R35GM119634-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167015. Licensed CC0.

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