RESEARCH: INFLUENZA
FOLDING PROJECT #18450 PROFILE

This project explores how miniproteins designed to fight the flu virus work. Scientists want to use computer simulations to understand how these tiny proteins bind to the virus and block its spread. This could help create even better antiviral 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

Small proteins engineered for specific functions.

Miniproteins are tiny proteins designed in a lab to perform specific tasks. They're smaller than regular proteins and can be used to treat diseases by blocking harmful molecules or triggering beneficial ones.

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therapeutics

Agents used to treat or prevent disease.

Therapeutics are medical treatments that aim to cure, prevent, or manage diseases. They include medications, therapies, and other interventions designed to improve health.

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infectious disease

Disease caused by pathogens.

Infectious diseases are illnesses caused by microorganisms such as bacteria, viruses, fungi, or parasites. They can spread from person to person or through contact with contaminated objects or environments.

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hemagglutinin

Viral protein that binds to sialic acid.

Hemagglutinin is a protein found on the surface of some viruses, like influenza. It helps the virus attach to and enter cells by binding to a sugar called sialic acid.

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H1 influenza A

Subtype of influenza A virus.

H1N1 is a type of influenza A virus that can cause seasonal flu. It's characterized by its hemagglutinin (HA) protein, which has the subtype designation 'H1'.

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monoclonal antibody

Lab-produced antibody targeting a specific antigen.

Monoclonal antibodies are laboratory-made proteins designed to target and bind to specific proteins called antigens. They're used in treating various diseases by blocking the action of harmful molecules or activating the immune system.

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affinity maturation

Process of increasing antibody binding affinity.

Affinity maturation is the process of improving an antibody's ability to bind to its target antigen. It involves making small changes to the antibody's structure, which can result in stronger and more specific binding.

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molecular dynamics simulations

Computer simulations of molecular movement.

Molecular dynamics simulations are computer models that simulate the motion of atoms and molecules over time. They're used to study how molecules interact with each other and their environment.