A sound strategy for homology modeling-based affinity maturation of a HIF-1α single-domain intrabody
Hu, M.; Kang, G.; Cheng, X.; Wang, J.; Li, R.; Bai, Z.; Yang, D.; Huang, H.
Show abstract
A sound strategy for computer-aided binding affinity prediction was developed for in silico nanobody affinity maturation. Venn-intersection of multi-algorithm screening (VIMAS), an iterative computer-assisted nanobody affinity maturation virtual screening procedure, was designed. Homology modeling and protein docking methods were used to substitute the need for solution of a complex crystal structure, which is expanding the application of this platform. As a test case, an anti-HIF-1 nanobody, VHH212, was screened via a native ribosome display library with a 26.6 nM of KD value was used as the parent. A mutant with a 17.5-fold enhancement in binding affinity (1.52 nM) was obtained by using the VIMAS strategy. Furthermore, the protein-protein interaction of interface residues, which is important for binding affinity, was analyzed in-depth. Targeting HIF-1 can sensitize PDAC tumors to gemcitabine, which is a potential co-treatment method for pancreatic cancer patients. Under combined treatment, the cytotoxicity of gemcitabine on pancreatic cancer cell lines increased with the enhanced-affinity of an intrabody. Thus, this study provides a platform for universal, efficient and convenient in silico affinity maturation of nanobodies.
Matching journals
The top 15 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A yeast two-hybrid system to obtain triple-helical ligands from combinatorial random peptide libraries 94%
- Designing monomeric IFNγ: the significance of domain-swapped dimer structure in IFNγ immune responses 94%
- Binding of single-mutant epidermal growth factor (EGF) ligands alter the stability of the EGF receptor dimer and promote growth signaling 94%
Similar papers in this journal
- De novo design of ATPase based on the blueprint optimized for harboring the P-loop motif 95%
- Revisiting the phosphotyrosine binding pocket of Fyn SH2 domain led to the Identification of novel SH2 superbinders 95%
- Thermostability and binding properties of single-chained Fv fragments derived from therapeutic antibodies 95%
Similar papers in this journal
Similar papers in this journal
- Discovery of Highly Active Kynureninases for Cancer Immunotherapy through Protein Language Model 93%
- Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease 93%
- Beyond DNA Binding: single C2H2 zinc fingers with adjacent β-strands mediate dimerization in Drosophila transcription factors 92%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.