Revisiting antibody modeling assessment for CDR-H3 loop
| Autor: | Narutoshi Kamiya, Hiroshi Nishigami, Haruki Nakamura |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Physics Work (thermodynamics) Sequence Heavy chain CDR-H3 loop Energy landscape Bioengineering multicanonical molecular dynamics simulation Crystal structure Biochemistry Loop (topology) Crystal 03 medical and health sciences free energy landscape 030104 developmental biology antibody Original Article Conformational sampling Biological system Molecular Biology crystal packing Biotechnology |
| Zdroj: | Protein Engineering, Design and Selection |
| ISSN: | 1741-0134 |
| Popis: | The antigen-binding site of antibodies, also known as complementarity-determining region (CDR), has hypervariable sequence properties. In particular, the third CDR loop of the heavy chain, CDR-H3, has such variability in its sequence, length, and conformation that ordinary modeling techniques cannot build a high-quality structure. At Stage 2 of the Second Antibody Modeling Assessment (AMA-II) held in 2013, the model structures of the CDR-H3 loops were submitted by the seven modelers and were critically assessed. After our participation in AMA-II, we rebuilt one of the long CDR-H3 loops with 13 residues (A52 antibody) by a more precise method, using enhanced conformational sampling with the explicit water model, as compared to our previous method employed at AMA-II. The current stable models obtained from the free energy landscape at 300 K include structures similar to the X-ray crystal structures. Those models were not built in our previous work at AMA-II. The current free energy landscape suggested that the CDR-H3 loop structures in the crystal are not stable in solution, but they are stabilized by the crystal packing effect. |
| Databáze: | OpenAIRE |
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