RESEARCH: INFLUENZA
FOLDING PROJECT #12458 PROFILE

Miniprotein drugs are a new type of treatment for diseases like the flu. This project uses computer simulations to understand how these miniproteins stick to the virus and block its ability to infect cells. This research could lead to better designed miniprotein drugs in the future.

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 with therapeutic potential.

Miniproteins are artificially engineered proteins that are smaller than traditional antibodies. They offer advantages such as easier production and delivery, making them promising candidates for treating various diseases.

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therapeutics

Substances used to treat diseases or medical conditions.

Therapeutics encompass a wide range of treatments, including medications, biologics, and gene therapies, aimed at preventing, diagnosing, and treating diseases.

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hemagglutinin

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

Hemagglutinin is a surface protein found on many viruses, including influenza. It plays a crucial role in the virus's ability to attach to and enter host cells.

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influenza A

A type of virus that causes seasonal flu.

Influenza A is a highly contagious respiratory virus responsible for causing seasonal influenza outbreaks. It has various subtypes based on the surface proteins hemagglutinin (HA) and neuraminidase (NA).

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H1

Subtype of influenza A virus.

H1 is a designation used to classify a specific subtype of the influenza A virus based on its hemagglutinin (HA) protein. It is one of the many subtypes that can cause seasonal flu.

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sialic acid

A type of sugar found on cell surfaces.

Sialic acid is a complex sugar molecule that plays a crucial role in various biological processes. It is often attached to proteins and lipids on the surface of cells, acting as a recognition site for viruses and other molecules.

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binding interface

The region on a protein where it interacts with other molecules.

The binding interface refers to the specific surface area on a protein molecule where it binds or interacts with other molecules, such as ligands, substrates, or other proteins.

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affinity maturation

The process of increasing the binding affinity of an antibody or other protein.

Affinity maturation is a crucial process in the immune system where antibodies are refined over time to bind more strongly to their target antigens. It involves genetic mutations that enhance the binding affinity.

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molecular dynamics simulations

Computer models that simulate the movement of atoms and molecules over time.

Molecular dynamics simulations are powerful computational tools used to study the behavior of molecules at an atomic level. They involve simulating the movements of atoms and bonds over time, providing insights into molecular interactions and processes.

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enhanced sampling methods

Techniques used to speed up molecular dynamics simulations.

Enhanced sampling methods are computational techniques employed in molecular dynamics simulations to overcome the limitations of traditional simulations. They aim to explore a wider range of conformations and accelerate the sampling of rare events.