RESEARCH: INFLUENZA
FOLDING PROJECT #18449 PROFILE

This project studies miniproteins designed to fight the flu. These tiny proteins latch onto a viral protein called hemagglutinin, stopping the virus from infecting cells. Scientists are using computer simulations to understand how these miniproteins work so they can design even better ones 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 engineered for specific functions.

Miniproteins are artificially created proteins that are much smaller than typical proteins. They have various applications in medicine, such as treating diseases and delivering drugs.

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therapeutics

Substances used to treat or prevent diseases.

Therapeutics are medical treatments used to address various health conditions. They can include medications, therapies, and other interventions aimed at preventing, diagnosing, or curing diseases.

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hemagglutinin

A viral protein that binds to sialic acid on cell surfaces.

Hemagglutinin is a protein found on the surface of influenza viruses. It helps the virus attach to and enter human cells. This binding process is crucial for the virus to infect and replicate.

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influenza A

A type of virus that causes seasonal flu.

Influenza A is a common respiratory virus that can cause mild to severe illness. It spreads easily through airborne droplets and can lead to complications like pneumonia.

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affinity maturation

The process of improving the binding affinity of a molecule.

Affinity maturation is a technique used to enhance the ability of molecules, such as antibodies or miniproteins, to bind to their target with higher specificity and strength. This process often involves iterative rounds of mutations and selection.

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molecular dynamics

A simulation method used to study the movement and interactions of molecules.

Molecular dynamics simulations are computer-based models that track the movement of atoms and molecules over time. They allow researchers to understand how molecules interact and behave under different conditions.

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enhanced sampling

A method used to accelerate molecular simulations.

Enhanced sampling techniques are used in molecular dynamics simulations to explore rare events and improve the efficiency of simulations. They allow researchers to study systems that would otherwise be too slow or complex to simulate.