Modelling of the HuCal Library VK1 Domain

A very simple case: one of the 14 Hucal (synthetic human combinatorial antibody library ) frameworks. The HuCal Library consists of 7 VL frameworks (4 kappa, 3 lambda) and 7 VH frameworks giving 49 different combinations covering a large part of the framework variability observed in human germline sequences and presenting convenient restriction sites for the randomization of all six CDR loops

The target sequence shows a very good fit to PDB template sequences: The best templates all fit with >=90% similarity (best: 2fgw: 94%similarity, 91%identity, but only 3.0 A resolution, therefore, the second best template (sequence fit: 90% ident. but 1.9Å resolution) was used for modelling

Comparison of multiple templates allow to assess the effects of point mutations=> all template structures agree very well to each other. Exceptions: outer loop of 1fvc,1fvd: G L66 replaced by R (FSGSGSGT to FSGSRSGT), leading to a "Kink" in the outer loop. CDR3 of 1dfb: no cis-Pro, shorter than usual.