Specific attributes of the VL domain influence both the structure and structural variability of CDR-H3 through steric effects
Guloglu, B.; Deane, C. M.
Show abstract
Antibodies, through their ability to target virtually any epitope, play a key role in driving the adaptive immune response in jawed vertebrates. The binding domains of standard antibodies are their variable light (VL) and heavy (VH) domains, both of which present analogous complementarity-determining region (CDR) loops. It has long been known that the VH CDRs contribute more heavily to the antigen-binding surface (paratope), with the CDR-H3 loop providing a major modality for the generation of diverse paratopes. Here, we provide evidence for an additional role of the VL domain as a modulator of CDR-H3 structure, using a diverse set of antibody crystal structures and a large set of molecular dynamics simulations. We show that specific attributes of the VL domain such as CDR canonical forms and genes can influence the structural diversity of the CDR-H3 loop, and provide a physical model for how this effect occurs through inter-loop contacts and packing of CDRs against each other. Our study provides insights into the interdependent nature of CDR conformations, an understanding of which is important for the rational antibody design process.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Induced fit with replica exchange improves protein complex structure prediction 94%
- Learning patterns of HIV-1 co-resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning 93%
- Exploring the Potential of Structure-Based Deep Learning Approaches for T cell Receptor Design 93%
Similar papers in this journal
Similar papers in this journal
- The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour 94%
- T Cell Receptor Non-Equilibrium Kinetics 94%
- HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state 93%
Similar papers in this journal
- Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as substrates for proteolytic maturation. 95%
- Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody 95%
- Peptide binding specificity prediction using fine-tuned protein structure prediction networks 95%
Similar papers in this journal
- Modeling Coronavirus Spike Protein Dynamics: Implications for Immunogenicity and Immune Escape 95%
- SARS-CoV-2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential 95%
- IP6 and PF74 affect HIV-1 Capsid Stability through Modulation of Hexamer-Hexamer Tilt Angle Preference 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.