# Metalloproteins: evolution, catalysis and material design

> **NIH NIH R35** · BAYLOR UNIVERSITY · 2024 · $235,959

## Abstract

Project 1: Recently, we have demonstrated for the first time the predictive link between NMR chemical
shift perturbation, protein dynamics and probability of finding productive mutations, which allowed us to create
an unnatural metalloenzyme with with a 107-fold improvement over the background rate and less than 100-fold
away from the diffusion limit. I propose to expand NMR-guided directed evolution to 1) utilize other protein
dynamics probing modalities to aaply the approach to larger proteins; 2) develop catalysts for practically useful
reactions; 3) develop of metal-binding proteins with high metal affinity. Results generated in the proposed work
will help advance fundamental understanding of the principles that define function in metalloproteins and drive
enzymatic activity. From the practical standpoint, this work will allow for creation of smaller functional proteins
capable of promoting chemical transformations and produce inexpensive and biocompatible protein catalysts
that could be easily handled in the applied setting for pesticide/chemical weapons remediation, DNA hydrolysis
and phenol oxidation. Project 2: I will develop new approaches to osteoarthritis treatment using smart, stimuli-
responsive, self-healing biocompatible antimicrobial hydrogels. In addition to direct biomedical application of the
designed hydrogel materials, structural models for the hydrogel assemblies will facilitate our understanding of
the mechanism of gelation of metallopeptides and will guide rational design of improved materials.
1

## Key facts

- **NIH application ID:** 10941277
- **Project number:** 1R35GM155013-01
- **Recipient organization:** BAYLOR UNIVERSITY
- **Principal Investigator:** OLGA MAKHLYNETS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $235,959
- **Award type:** 1
- **Project period:** 2024-09-05 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941277

## Citation

> US National Institutes of Health, RePORTER application 10941277, Metalloproteins: evolution, catalysis and material design (1R35GM155013-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10941277. Licensed CC0.

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