Antibody maturation

Antibodies undergo a process called maturation in which they undergo a series of mutations as they “learn” how to recognize molecules foreign to our body. We’d love to be able to engineer new antibodies, but that has proven remarkably challenging.

It’s possible that by understanding how the dynamics of antibodies change during their maturation pathway, we could improve our ability to engineer these molecules. 

In projects p18265-18274 we have been working to understand how antibody dynamics change during maturation. We ended up generating over 8.5 milliseconds of simulation, approximately 2 orders of magnitude of simulation more than other datasets that we’re aware of.

The dominant view has been that antibodies undergo stabilization during the maturation pathway. That is, mature antibodies are more rigid than less mature antibodies.

We find a more nuanced picture: the dynamics of various parts of the antibody are tuned differently depending on what they do. Parts of the antibody that directly bind the antigen do tend to become more ridig. However, parts of the antibody that bind sugar molecules called glycans actually tend to become more dynamic.

We expect these results should enable improved engineering of high affinity antibodies for a variety of challenging targets including HIV and flu proteins.

A huge thank you to everyone who has contributed their time and energy to these projects!