Rational affinity enhancement of fragmented antibody by ligand-based affinity improvement approach.

Rational affinity enhancement of fragmented antibody by ligand-based affinity improvement approach.
Biochem Biophys Res Commun. 2018 Nov 30;506(3):653-659
Authors: Ebrahimi Z, Asgari S, Ahangari Cohan R, Hosseinzadeh R, Hosseinzadeh G, Arezumand R
Abstract
Antibody engineering is now a noteworthy area in biopharmaceuticals as the next generation of marketed antibodies is engineered antibodies such as affinity- or stability-improved antibodies, fragmented or fused antibodies, antibody drug conjugates (ADCs), and PEGylated antibody fragments. In the current study, affinity enhancement of Nb against PlGF was performed by an in silico affinity maturation and molecular dynamics (MD) simulation. First, 300 single-point mutants were designed by identifying the residues involved in interaction with PlGF and different energy distributions. An energy based screening was performed to select best single-point mutants. Additionally, one variant containing two mutations was designed based on the selected single-point mutants. Finally, mutants-PlGF complexes were analyzed in details by all atom MD simulation. Trajectory analysis revealed that in both single (L112H, S31D, A97K, and R45E) and double (S31D & R45E) mutants, the free binding energies and the stability of complexes were significantly improved. The highest increment in affinity was observed for S31D mutant due to substantial increase in polar and electrostatic interactions. The second...

Source: Biochemical and Biophysical Research communications - November 22, 2018 Category: Biochemistry Authors: Ebrahimi Z, Asgari S, Ahangari Cohan R, Hosseinzadeh R, Hosseinzadeh G, Arezumand R Tags: Biochem Biophys Res Commun Source Type: research