The H3 loop of antibodies shows unique structural characteristics
The H3 loop in the Complementary Determining Region (CDR) of antibodies plays a key role in their ability to bind the diverse space of potential antigens. It is also exceptionally difficult to model computationally causing a significant hurdle for in-silico development of antibody biotherapeutics....
| Main Authors: | , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Wiley
2017
|
| _version_ | 1797086867818020864 |
|---|---|
| author | Regep, C Georges, G Shi, J Popovic, B Deane, C |
| author_facet | Regep, C Georges, G Shi, J Popovic, B Deane, C |
| author_sort | Regep, C |
| collection | OXFORD |
| description | The H3 loop in the Complementary Determining Region (CDR) of antibodies plays a key role in their ability to bind the diverse space of potential antigens. It is also exceptionally difficult to model computationally causing a significant hurdle for in-silico development of antibody biotherapeutics. In this paper we show that most H3s have unique structural characteristics which may explain why they are so challenging to model. We found that over 75% of H3 loops do not have a sub-Angstrom structural neighbour in the non-antibody world. Also, in a comparison with a non-redundant set of all protein fragments over 30% of H3 loops have a unique structure, with the average for all of other loops being less than 3%. We further observed that this structural difference can be seen at the level of four residue fragments where H3 loops present numerous novel conformations, and also at the level of individual residues with Tyrosine and Glycine often found in energetically unfavourable conformations. |
| first_indexed | 2024-03-07T02:28:05Z |
| format | Journal article |
| id | oxford-uuid:a64f36e8-740a-435b-801f-139720c920fb |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:28:05Z |
| publishDate | 2017 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:a64f36e8-740a-435b-801f-139720c920fb2022-03-27T02:46:21ZThe H3 loop of antibodies shows unique structural characteristicsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a64f36e8-740a-435b-801f-139720c920fbSymplectic Elements at OxfordWiley2017Regep, CGeorges, GShi, JPopovic, BDeane, CThe H3 loop in the Complementary Determining Region (CDR) of antibodies plays a key role in their ability to bind the diverse space of potential antigens. It is also exceptionally difficult to model computationally causing a significant hurdle for in-silico development of antibody biotherapeutics. In this paper we show that most H3s have unique structural characteristics which may explain why they are so challenging to model. We found that over 75% of H3 loops do not have a sub-Angstrom structural neighbour in the non-antibody world. Also, in a comparison with a non-redundant set of all protein fragments over 30% of H3 loops have a unique structure, with the average for all of other loops being less than 3%. We further observed that this structural difference can be seen at the level of four residue fragments where H3 loops present numerous novel conformations, and also at the level of individual residues with Tyrosine and Glycine often found in energetically unfavourable conformations. |
| spellingShingle | Regep, C Georges, G Shi, J Popovic, B Deane, C The H3 loop of antibodies shows unique structural characteristics |
| title | The H3 loop of antibodies shows unique structural characteristics |
| title_full | The H3 loop of antibodies shows unique structural characteristics |
| title_fullStr | The H3 loop of antibodies shows unique structural characteristics |
| title_full_unstemmed | The H3 loop of antibodies shows unique structural characteristics |
| title_short | The H3 loop of antibodies shows unique structural characteristics |
| title_sort | h3 loop of antibodies shows unique structural characteristics |
| work_keys_str_mv | AT regepc theh3loopofantibodiesshowsuniquestructuralcharacteristics AT georgesg theh3loopofantibodiesshowsuniquestructuralcharacteristics AT shij theh3loopofantibodiesshowsuniquestructuralcharacteristics AT popovicb theh3loopofantibodiesshowsuniquestructuralcharacteristics AT deanec theh3loopofantibodiesshowsuniquestructuralcharacteristics AT regepc h3loopofantibodiesshowsuniquestructuralcharacteristics AT georgesg h3loopofantibodiesshowsuniquestructuralcharacteristics AT shij h3loopofantibodiesshowsuniquestructuralcharacteristics AT popovicb h3loopofantibodiesshowsuniquestructuralcharacteristics AT deanec h3loopofantibodiesshowsuniquestructuralcharacteristics |