Scholars@Duke
Homme Wytzes Hellinga

Homme Wytzes Hellinga

James B. Duke Distinguished Professor of Biochemistry
Biochemistry
hwh@biochem.duke.edu
Duke Box 3711, Room 413D, Durham, NC 27710
413D Nanaline H Duke, Research Drive, Durham, NC 27708

Overview

The work in this laboratory takes a combined theoretical and experimental approach to problems in structural biophysics. Computer simulations play an increasingly important role in our understanding of protein folding, stability, activity, and the specificity of protein-ligand interactions. Design methods are being developed which can be used to rationally modify the structure and function of a protein. This design methodology allows us to ask very specific question firmly based on a theoretical understanding of the system, which can then be put to an experimental test. The experimental work involves molecular biology to construct genes for the designed proteins, protein purification methods and a variety of physical techniques t o study the activity, stability and structure of the designed proteins. Each design goes through several cycles of iterative improvement involving design, analysis, redesign, etc. Empirical improvement methods such as genetic selection are also used where possible.
We have developed and experimentally validated a variety of different computer algorithms that allow us to design biologically active receptors, sensors, and enzymes. This has allowed us to build novel biosensors to detect analytes of clinical (metabolites, drugs), environmental (pollutants), military and homeland defense interest (chemical or biological threats). We have also developed synthetic signal transduction pathways and genetic circuits that enable bacteria to report xenobiotics in their immediate environment via responses triggered with computationally designed receptors ("biological sentinels"). Other applications include the design of novel enzymes, and chemically controlled molecular motors that can be used in bionanotechnology.

Current Appointments & Affiliations

James B. Duke Distinguished Professor of Biochemistry · 2005 - Present Biochemistry, Basic Science Departments
Professor of Biochemistry · 2004 - Present Biochemistry, Basic Science Departments

Recent Publications

Accurate Identification of Periplasmic Urea-binding Proteins by Structure- and Genome Context-assisted Functional Analysis.

Journal Article J Mol Biol · November 15, 2024 ABC transporters are ancient and ubiquitous nutrient transport systems in bacteria and play a central role in defining lifestyles. Periplasmic solute-binding proteins (SBPs) are components that deliver ligands to their translocation machinery. SBPs have di ... Full text Link to item Cite

Chromophore carbonyl twisting in fluorescent biosensors encodes direct readout of protein conformations with multicolor switching.

Journal Article Commun Chem · August 19, 2023 Fluorescent labeling of proteins is a powerful tool for probing structure-function relationships with many biosensing applications. Structure-based rules for systematically designing fluorescent biosensors require understanding ligand-mediated fluorescent ... Full text Link to item Cite

Thermally controlled intein splicing of engineered DNA polymerases provides a robust and generalizable solution for accurate and sensitive molecular diagnostics.

Journal Article Nucleic Acids Res · June 23, 2023 DNA polymerases are essential for nucleic acid synthesis, cloning, sequencing and molecular diagnostics technologies. Conditional intein splicing is a powerful tool for controlling enzyme reactions. We have engineered a thermal switch into thermostable DNA ... Full text Link to item Cite
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Recent Grants

Structure and Mechanism of Protein Prenyltransferases

ResearchCollaborator · Awarded by National Institutes of Health · 1995 - 2016

Structural biology of human DNA mismatch repair machinery

ResearchCollaborator · Awarded by National Institutes of Health · 2009 - 2012

NIH Director's Pioneer Award

ResearchPrincipal Investigator · Awarded by National Institutes of Health · 2004 - 2010

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Education, Training & Certifications

University of Cambridge (United Kingdom) · 1986 Ph.D.