De Novo Antibody Design

Computational antibody engineering efforts have focused on improving binding affinities or biophysical characteristics. De novo design of antibodies binding specific epitopes could greatly accelerate the discovery of therapeutics as compared to conventional immunization or synthetic library selection strategies. Creative Biolabs is dedicated to establishing the most exquisite service platform for our clients and the antibody development services can provide comprehensive technical support for advancing our clients’ projects.

De Novo Design

Antibody-antigen interactions are dominated by the complementarity determining regions (CDRs), three on each of the heavy and light variable domains. Typically, CDRs bind antigens by forming a shape-complementary pocket with favorable interactions distributed throughout the CDRs. Owing to the high degree of structural homology between variable domains from different antibodies, and in particular to the fact that most CDR loops can be clustered into canonical conformations, the vast majority of the Fv region can now be modeled reliably and with high accuracy. Scientists have developed the OptCDR method and the OptMAVEn method, which extends the applicability of the earlier OptCDR approach to the de novo design of the whole Fv region.

OptMAVEn consists of a combinatorial-design procedure that essentially reproduces the immune-system V(D)J recombination, followed by an energy-based in silico affinity maturation inspired by the somatic hypermutation mechanism. The OptMAVEn pipeline can be split into four steps.

• The first step is the sampling of the antigen positions into a predefined antibody binding site.
• Antigen-positioning is followed by the assignment of the best V, (D), and J antibody modular parts selected from the MAPs database, thus leading to the assembly of germline-antibody models for the target of interest.
• The third step consists in all-atom, explicit-solvent, 100 ns molecular dynamics simulations carried out for each model.
• The fourth and final step is an in silico affinity maturation, during which mutations in the antibody are selected to improve the binding energy.

Fig.1 Schematic representations of de novo antibody design.

The Services

The high specificity and binding affinity of antibodies with antigens enable them to be used as therapeutic agents for the treatment of different diseases. Traditional antibody design methods are effective but they remain time consuming, cannot target a specific epitope, and are unable to tolerate rapid changes of antigens. Computational methods for the de novo design of a fully human antibody against any specific antigen provide a route to resolve these issues. This strategy could offer a general route to therapeutic antibodies for many pathogens that have resisted traditional vaccine development, including highly antigenically-variable viruses such as HIV, influenza, and Ebola virus. Therefore, we can offer this novel antibody design service to meet specific customer requirements.

Creative Biolabs has focused on the development of drug discovery for years, we whole-heartedly cooperate with you to accomplish our shared goals. Our team provides you with outstanding support and meets your specific needs with a professional technology platform. If you are interested in our services, please feel free to contact us or directly sent us an inquiry.

For Research Use Only.