RESEARCH: INFLUENZA
FOLDING PROJECT #12430 PROFILE

This project looks at miniprotein drugs that fight the flu virus. These tiny proteins latch onto a part of the virus called hemagglutinin, preventing it from infecting cells. Scientists want to use computer simulations to understand how these miniproteins work and design even better ones.

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 designed for therapeutic purposes.

Miniproteins are tiny proteins engineered to act as drugs. They're smaller than traditional antibodies but larger than small molecule drugs, offering a unique approach to treating diseases.

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therapeutics

Substances used to treat or prevent diseases.

Therapeutics encompass a wide range of medical treatments, including drugs, vaccines, and gene therapies, aimed at preventing, diagnosing, or treating diseases.

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hemagglutinin

A viral protein that allows influenza A virus to bind to cell surfaces.

Hemagglutinin is a key protein on the surface of the influenza A virus. It helps the virus attach to and infect cells by binding to sialic acid molecules present on cell surfaces.

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influenza A (HA)

Hemagglutinin (HA) subtype of Influenza A virus.

Influenza A viruses are classified based on their surface proteins, hemagglutinin (HA) and neuraminidase (NA). HA allows the virus to bind to cells while NA helps it spread.

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binding

The process of molecules adhering to each other.

Binding refers to the interaction between molecules, such as proteins and ligands, where they attach to each other. This can be a reversible or irreversible process and is crucial for many biological functions.

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affinity maturation

The process of enhancing the binding affinity of antibodies.

Affinity maturation is a biological process where antibodies are gradually improved over time to bind more strongly to their target antigens. This is crucial for effective immune responses.

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molecular dynamics simulations

Computer simulations used to model the movement of atoms and molecules.

Molecular dynamics simulations are powerful tools that allow scientists to virtually observe and analyze the behavior of molecules over time. They help understand complex biological processes at a detailed atomic level.

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ab initio

From first principles; based on fundamental laws of physics.

Ab initio methods in computational chemistry rely solely on the fundamental laws of physics to predict molecular properties and behavior. They provide a theoretical foundation for understanding chemical systems.