20.500.12556/RUNG-2698
Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies
Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular
recognition. Their small size represents a precious advantage for rational mutagenesis based on
modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate
mutations by developing a simulation protocol based on all-atom molecular dynamics and wholemolecule
docking. The method was tested on two sets of nanobodies characterized experimentally
for their biophysical features. One set contained point mutations introduced to humanize a wild type
sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae
and human hallmarks. The method resulted in accurate scoring approaches to predict experimental
yields and enabled to identify the structural modifications induced by mutations. This work is a
promising tool for the in silico development of single-domain antibodies and opens the opportunity to
customize single functional domains of larger macromolecules
nanobodies
molecular dynamics
modeling
antibody solubility
true
true
false
Angleški jezik
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2016-10-11 08:39:54
2016-10-11 11:24:13
2023-06-09 03:18:17
0000-00-00 00:00:00
2016
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11
6:34869 |
2016
0000-00-00
Zaloznikova
NiDoloceno
NiDoloceno
0000-00-00
0000-00-00
0000-00-00
4531707
10.1038/srep34869
URN:SI:UNG:REP:LFCPDQKV
Soler_et_al-2016-Scientific_Reports.pdf
Soler_et_al-2016-Scientific_Reports.pdf
1
8FFF6923296A39E23851D624572720B9
025ddf439151543a119889819f6d21583030a992f6b3764fdb8f631f01c14332
1dd27401-05ce-11ee-9c48-5ef991fed68f
https://repozitorij.ung.si/Dokument.php?lang=slv&id=4734
Univerza v Novi Gorici
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