RESEARCH: INFLUENZA
FOLDING PROJECT #12437 PROFILE

This project studies miniproteins that block the flu virus. Scientists want to understand how these miniproteins bind to the virus and improve their design using computer simulations. This will help create better treatments for influenza.

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 therapeutic use.

Miniproteins are artificially created proteins designed to have specific functions. They are smaller than traditional antibodies and offer potential advantages in drug delivery and efficacy. In this context, miniproteins are being explored as a new type of treatment for infectious diseases.

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therapeutics

Substances used to treat or prevent diseases.

Therapeutics encompass a wide range of medical treatments designed to address various health conditions. This includes medications, therapies, and other interventions aimed at curing, preventing, or managing diseases.

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infectious disease

A disease caused by the invasion and multiplication of microorganisms.

Infectious diseases are illnesses caused by pathogens like bacteria, viruses, fungi, or parasites. These organisms can spread from person to person, animal to person, or through contaminated environments. Examples include influenza, tuberculosis, and HIV/AIDS.

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hemagglutinin

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

Hemagglutinin (HA) is a key protein found on the surface of influenza A viruses. It plays a crucial role in infection by binding to sialic acid receptors on human cells, allowing the virus to attach and enter. HA is also involved in other processes during viral replication and spread.

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influenza A (HA)

Hemagglutinin protein of influenza A virus

Influenza A (HA) refers to the hemagglutinin protein found in the influenza A virus. This protein is responsible for allowing the virus to attach to and infect human cells.

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affinity maturation

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

Affinity maturation is a key step in developing effective drugs and therapies. It involves enhancing the ability of a molecule, such as a miniprotein, to bind tightly to its intended target, improving its efficacy.

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molecular dynamics simulations

Computer simulations used to study the motion and interactions of molecules.

Molecular dynamics simulations are powerful tools used in computational biology to model the behavior of molecules. They allow researchers to visualize how molecules interact, move, and change shape over time.

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enhanced sampling methods

Techniques used to accelerate molecular dynamics simulations and explore rare events.

Enhanced sampling methods are computational tools that improve the efficiency of molecular dynamics simulations. They help researchers overcome limitations in exploring complex systems and uncover rare events that would be difficult to observe through standard simulations.