RESEARCH: ANTIBODY-DYNAMICS-SIMULATION
FOLDING PROJECT #18269 PROFILE

This project simulates how antibodies change and get better at fighting infections. They're looking at real antibody examples and using computer models to see how different changes affect their ability to grab onto germs. This could help scientists design new, more effective medicines and vaccines.

Note: This TLDR is a simplication and may not be 100% accurate.

In their response to antigens, antibodies undergo a process called affinity maturation where they pick up mutations that help increase their affinity for the antigen.

This is an integral part of the humoral immune response.

There are tools to decode what these mutations are, but the role of these mutations in influencing antibody dynamics remains largely unclear.

Understanding how antibody dynamics change throughout the course of affinity maturation would help in designing highly specific antibody therapeutics and vaccine immunogens.
This project aims to simulate a range of antibody affinity maturation pathways.

We have multiple lineages we would like to track.

These are all lineages that have led to potent antibodies and have published structures available.

For each lineage, we are simulating a naïve antibody and a mature antibody.

Similar studies conducted in the past have used short
simulations and have simulated only the variable regions of the proteins.

Here, we will generate large simulation datasets that include the constant regions as well as the variable regions, giving us a more accurate glimpse into antibody dynamics.

Our hope is that these simulations will uncover the dynamics that are responsible for highly specific and potent antibodies, helping to improve antibody design in the future.
p18265 – PGT121 lineage, naïve antibody.

The PGT121 lineage antibodies
are broadly neutralizing antibodies that bind to the V3-glycan epitope on
the HIV envelope protein gp120.
p18266 – PGT121 lineage, mature antibody.

The PGT121 lineage antibodies
are broadly neutralizing antibodies that bind to the V3-glycan epitope on
the HIV envelope protein gp120.
p18267 – CAP256-VRC26 lineage, naïve antibody.

The CAP256-VRC26
lineage antibodies are broadly neutralizing antibodies that bind to the V2-
apex epitope on the HIV envelope protein gp120.
p18268 – CAP256-VRC26, mature antibody.

The CAP256-VRC26 lineage
antibodies are broadly neutralizing antibodies that bind to the V2-apex
epitope on the HIV envelope protein gp120.
p18569 – CH65-CH67 lineage, naïve antibody.

The CH65-CH67 lineage
antibodies bind to the receptor binding site on the influenza hemagglutinin
protein. p18270 – CH65-CH67 lineage, mature antibody.

The CH65-CH67 lineage
antibodies bind to the receptor binding site on the influenza hemagglutinin
protein.
p18271 – CH103 lineage, naïve antibody.

The CH103 lineage antibodies are
broadly neutralizing antibodies that bind to the CD4 binding site epitope on
the HIV envelope protein gp120.
p18272 – CH103 lineage, mature antibody.

The CH103 lineage antibodies
are broadly neutralizing antibodies that bind to the CD4 binding site epitope
on the HIV envelope protein gp120.
p18273 – 1-18 lineage, naïve antibody.

The 1-18 lineage antibodies bind to
the CD4 binding site on the HIV envelope protein gp120.
p18274 – 1-18 lineage, mature antibody.

The 1-18 lineage antibodies are
broadly neutralizing antibodies that bind to the CD4 binding site on the HIV
envelope protein gp120.

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antibody

A protein produced by the immune system to fight infections.

Antibodies are specialized proteins made by our immune system to identify and neutralize harmful substances like viruses and bacteria. They work by binding to specific targets on these invaders, marking them for destruction or preventing them from causing damage.

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affinity maturation

The process by which antibodies become more effective at binding to their target antigens.

Affinity maturation is a key step in the immune response where antibodies gradually improve their ability to recognize and bind to specific pathogens. This happens through mutations that enhance the antibody's binding strength, making it more effective at neutralizing the threat.

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antigen

A molecule that triggers an immune response.

Antigens are substances, often found on the surface of pathogens like viruses or bacteria, that our immune system recognizes as foreign. When our body encounters an antigen, it mounts a defense to eliminate it.

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mutations

Changes in the DNA sequence.

Mutations are alterations in the genetic code that can lead to variations in an organism's traits. These changes can be spontaneous or induced by environmental factors and play a crucial role in evolution and disease.

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lineage

A series of related antibodies that evolved from a common ancestor.

In immunology, a lineage refers to a group of antibodies descended from a single ancestral antibody. These antibodies share similarities in their structure and function, reflecting their evolutionary history.

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HIV

Human Immunodeficiency Virus

HIV is a retrovirus that attacks the body's immune system, specifically targeting CD4+ T cells. This weakens the immune response, making individuals susceptible to opportunistic infections and cancers.

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gp120

Glycoprotein 120, a protein on the surface of the HIV virus.

Gp120 is a key protein found on the outer envelope of the HIV virus. It plays a crucial role in attaching to and entering human cells, initiating infection.

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V3-glycan epitope

A specific sugar-protein structure on the gp120 protein that is recognized by certain antibodies.

The V3-glycan epitope is a unique binding site on the HIV gp120 protein. Antibodies targeting this epitope can effectively neutralize the virus.

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broadly neutralizing antibodies

Antibodies that can neutralize a wide range of different HIV strains.

Broadly neutralizing antibodies are a highly sought-after class of antibodies because they have the potential to provide long-lasting protection against HIV infection. They can target conserved regions on the virus, making them effective against diverse strains.