Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies.

ABSTRACT: 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 whole-molecule 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 identi

SUBMITTER: Soler MA 

PROVIDER: S-EPMC5056509 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature