RESEARCH: INFLUENZA
FOLDING PROJECT #12428 PROFILE

This project looks at how miniprotein drugs work against the flu virus. Miniproteins are like tiny antibodies that block the flu from attaching to cells. Researchers want to use computer simulations to figure out exactly how these miniproteins work and how to make them even better at fighting the flu.

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 with specific functions.

Miniproteins are engineered proteins smaller than traditional antibodies. They offer a bridge between large antibody drugs and simpler small molecule drugs. Their compact size allows for easier production and targeting of specific molecules like viruses.

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Therapeutics

Medicines or treatments designed to prevent or cure diseases.

Therapeutics encompass a broad range of medical treatments, including drugs, biologics, and gene therapies. They aim to diagnose, treat, or prevent illnesses.

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Hemagglutinin

A viral protein that binds to sialic acid receptors on host cells.

Hemagglutinin is a key protein found on the surface of influenza viruses. It allows the virus to attach to and enter human cells by binding to sialic acid molecules present on cell surfaces.

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H1

Subtype of influenza A virus.

H1 refers to a specific subtype of the influenza A virus. It is one of many subtypes classified based on their surface proteins, hemagglutinin (H) and neuraminidase (N).

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Influenza A

A type of influenza virus that can cause seasonal epidemics and pandemics.

Influenza A is a highly contagious respiratory virus responsible for flu outbreaks worldwide. It can cause a range of symptoms, including fever, cough, sore throat, and muscle aches.

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Monoclonal Antibody

A laboratory-produced antibody that recognizes and binds to a specific antigen.

Monoclonal antibodies are engineered immune proteins designed to target specific antigens, such as viral proteins or cancer cells. They are used in various medical treatments, including autoimmune diseases and cancer.

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Affinity Maturation

The process of improving the binding affinity of a molecule to its target.

Affinity maturation involves modifying a molecule, often an antibody or protein, to enhance its ability to bind to its intended target. This process is crucial for developing effective drugs and therapies.

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Molecular Dynamics

A computational method for simulating the movement of atoms and molecules over time.

Molecular dynamics simulations use computer algorithms to model the interactions between atoms and molecules. This allows researchers to study the structure and behavior of biological systems at a microscopic level.

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Enhanced Sampling

A technique used in molecular dynamics simulations to accelerate the exploration of complex conformational landscapes.

Enhanced sampling methods are employed in molecular dynamics simulations to overcome limitations in exploring rare events or conformations. They help researchers gain insights into dynamic processes that are difficult to observe through traditional simulations.