RESEARCH: ANTIBODY-DYNAMICS-SIMULATION
FOLDING PROJECT #18265 PROFILE

This project uses computer simulations to study how antibodies change over time to become better at fighting infections. By looking at real-life antibody examples, researchers hope to learn how to design even more effective treatments 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.
p18269 – 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 bodies to defend against harmful invaders like bacteria and viruses. They work by recognizing and attaching to specific targets on these invaders, marking them for destruction.

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Antigen

A molecule that triggers an immune response.

Antigens are like flags on invaders that signal to our immune system. They can be parts of bacteria, viruses, or even our own cells when they become abnormal.

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Affinity Maturation

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

Affinity maturation is like a training process for our immune system. When exposed to an antigen, our body produces many different antibodies. Over time, those that bind best are selected and multiplied, making the immune response stronger.

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Humoral Immune Response

An immune response mediated by antibodies.

The humoral immune response is one way our body fights infection. It involves B cells producing antibodies that target and neutralize pathogens.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the immune system, weakening the body's ability to fight off infections and diseases. It can lead to AIDS if left untreated.

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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 attaching to and entering human cells.

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Broadly Neutralizing Antibodies

Antibodies that can effectively neutralize multiple strains of a virus.

Broadly neutralizing antibodies are highly effective in fighting infections because they can target different parts of the virus.

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V3-glycan Epitope

A specific site on the gp120 protein of HIV that is recognized by certain antibodies.

The V3-glycan epitope is a key target for some broadly neutralizing antibodies. By binding to this site, these antibodies can prevent HIV from entering human cells.

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V2-apex Epitope

Another specific site on the gp120 protein of HIV that is recognized by certain antibodies.

The V2-apex epitope is another target for some broadly neutralizing antibodies. These antibodies can also block HIV from entering human cells.