RESEARCH: ANTIBODY-MATURATION-SIMULATION
FOLDING PROJECT #18274 PROFILE

The project simulates how antibodies evolve to become stronger at fighting viruses. They're using computer models to track changes in antibodies that target HIV and see how these changes make them more effective. This could help scientists design better 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.
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 neutralize harmful substances like bacteria and viruses.

Antibodies are specialized proteins created by our immune system to fight off infections. They latch onto specific invaders (antigens) and mark them for destruction by other immune cells. This helps our bodies stay healthy and protected.

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Affinity Maturation

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

Affinity maturation is like a training program for antibodies. During an immune response, antibodies are constantly changing and evolving. Through random mutations, some antibodies become better at grabbing onto the specific invaders (antigens) they're targeting. This makes them more effective at fighting off infections.

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Antigen

A molecule that triggers an immune response.

Antigens are like the 'Wanted' posters of the immune system. They are molecules found on the surface of bacteria, viruses, or other foreign substances. When our immune system recognizes an antigen as harmful, it launches a response to fight it off.

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gp120

Glycoprotein 120

gp120 is a protein found on the surface of the HIV virus. It's responsible for binding to receptors on human cells, allowing the virus to enter and infect them.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the body's immune system, specifically targeting CD4+ T cells. Over time, HIV can weaken the immune system to the point where it can no longer fight off infections and diseases, leading to AIDS.

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Broadly Neutralizing Antibodies

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

Broadly neutralizing antibodies are like superheroes of the immune system. They can fight off many different versions of a virus because they target highly conserved parts of the virus's structure. This makes them valuable tools for developing new treatments and vaccines.

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V3-glycan Epitope

A specific region on the gp120 protein of HIV that antibodies can bind to.

The V3-glycan epitope is a vulnerable spot on the HIV virus. Antibodies that target this area can block the virus from attaching to and entering human cells.

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V2-apex Epitope

A specific region on the gp120 protein of HIV that antibodies can bind to.

The V2-apex epitope is another vulnerable spot on the HIV virus. Antibodies that target this area can also block the virus from attaching to and entering human cells.