RESEARCH: ANTIBODY-DYNAMICS-SIMULATION
FOLDING PROJECT #18270 PROFILE

The project simulates how antibodies change to become better at fighting germs. Researchers will track antibody changes in powerful HIV-fighting antibodies to understand how they work so well. This could help 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 off pathogens.

Antibodies are specialized proteins created by our immune system to target and neutralize harmful invaders like bacteria, viruses, and fungi. They bind to specific parts of these pathogens (called antigens) and help eliminate them.

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Affinity Maturation

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

Affinity maturation is a crucial step in the immune response. When our body encounters a new pathogen, our immune system produces antibodies that initially have a low affinity for the pathogen's antigens. Through repeated exposure and selection, antibodies with higher affinities are generated, becoming more effective at neutralizing the threat.

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Antigen

A molecule that triggers an immune response.

Antigens are essentially the 'red flags' that alert our immune system to the presence of a potential threat. They can be found on the surface of pathogens like bacteria and viruses, or even on harmless substances like pollen.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the body's immune system. It destroys CD4+ T cells, which are essential for fighting off infections. Over time, HIV can lead to AIDS (Acquired Immunodeficiency Syndrome), a condition in which the immune system is severely weakened.

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gp120

Glycoprotein 120

gp120 is a protein found on the surface of the HIV virus. It plays a crucial role in helping the virus attach to and enter host cells.

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Broadly Neutralizing Antibodies

Antibodies that can neutralize a wide range of different strains or variants of a pathogen.

Broadly neutralizing antibodies (bNAbs) are highly sought-after because they can provide protection against multiple versions of a virus or bacterium. This is particularly important for viruses like HIV, which mutate rapidly and can develop resistance to conventional treatments.

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V3-glycan Epitope

A specific region on the HIV envelope protein gp120 that is targeted by some antibodies.

The V3-glycan epitope is a crucial binding site for certain antibodies. Targeting this region can help prevent HIV from attaching to and entering host cells.

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V2-apex Epitope

A specific region on the HIV envelope protein gp120 that is targeted by some antibodies.

The V2-apex epitope is another key binding site for certain antibodies. Targeting this region can also help block HIV infection.