Variable regions can adopt multiple interchain orientations, and these are difficult to predict

Summary

MD simulations suggest that tilt angle in the variable region of antibodies are coupled to CDR conformations. They are particularly affected by CDRL2, CDRH1, and CDRH3 (1). Anecdotally, these are very difficult to predict using programs such as Rosetta.

See also

• Loops from one V-region chain affect the conformations and dynamics of loops in the other chain

1.

Fernández-Quintero ML, Pomarici ND, Math BA, Kroell KB, Waibl F, Bujotzek A, et al. Antibodies exhibit multiple paratope states influencing VH–VL domain orientations. Communications Biology. 2020;3(1). Available from: https://doi.org/10.1038/s42003-020-01319-z