RESEARCH: INFLUENZA
FOLDING PROJECT #12427 PROFILE

This project looks at miniproteins designed to fight the flu. These tiny proteins bind to a part of the flu virus called hemagglutinin, stopping it from infecting cells. Scientists want to understand how these proteins work so well by using computer simulations to see how they attach and detach from the virus.

Note: This TLDR is a simplication and may not be 100% accurate.

Designed miniprotein therapeutics occupy the middle ground between small molecule drugs and monoclonal antibody treatments for infectious disease.

Hemagglutinin is a viral fusion protein that allows H1 influenza A (HA) to bind sialic acid on cell surfaces, as well as being involved in the post-endocytosis mechanism of cellular infection.; The Baker lab at University of Washington has developed de novo designed miniproteins that bind hemagglutinin, and developed ways to improve their binding through affinity maturation.

Many of the mutations seen in affinity-matured sequences are not directly in the binding interface, and it is unclear how these changes lead to higher affinity.

Understanding this mechanism may help us better computationally design better binders.

We aim to use molecular dynamics simulations to examine ab initio binding pathways for these miniprotein binders, and use enhanced sampling methods to study the unbinding reaction.

Pairing these methods together will provide a robust description of the complete binding reaction for this system.

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Miniprotein

A small protein engineered for specific functions.

Miniproteins are artificially designed proteins that are smaller than traditional antibodies. They have potential applications in medicine as targeted drug delivery systems or therapeutic agents due to their ability to bind to specific molecules.

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Hemagglutinin

A viral protein that allows viruses to bind to host cells.

Hemagglutinin is a surface protein found on influenza viruses. It plays a crucial role in the virus's ability to attach to and infect human cells by binding to sialic acid receptors on cell surfaces.

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Affinity Maturation

A process of increasing the binding affinity of an antibody or protein to its target.

Affinity maturation is a technique used in biotechnology to enhance the ability of antibodies or proteins to bind to their specific targets. This process involves making multiple rounds of mutations and selecting for variants with improved binding strength.

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Molecular Dynamics Simulations

Computer simulations of the movement and interactions of molecules.

Molecular dynamics simulations are a powerful tool used in computational biology to study the behavior of molecules over time. By simulating the movements and interactions of atoms and molecules, scientists can gain insights into their structure, function, and reactivity.

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Enhanced Sampling Methods

Techniques used to speed up molecular dynamics simulations.

Enhanced sampling methods are computational techniques used in molecular dynamics simulations to explore a wider range of possible conformations and reactions. These methods help overcome the limitations of traditional simulations by accelerating the exploration of the system's energy landscape.