%0 Journal Article
%T Molecular Recognition between A¦Â-Specific Single-Domain Antibody and A¦Â Misfolded Aggregates
%A Buyong Ma
%A Jie Zheng
%A Mingzhen Zhang
%A Ruth Nussinov
%J -
%D 2018
%R https://doi.org/10.3390/antib7030025
%X Abstract A¦Â is the toxic amyloid polypeptide responsible for Alzheimer¡¯s disease (AD). Prevention and elimination of the A¦Â misfolded aggregates are the promising therapeutic strategies for the AD treatments. Gammabody, the A¦Â-Specific Single-domain (VH) antibody, recognizes A¦Â aggregates with high affinity and specificity and reduces their toxicities. Employing the molecular dynamics simulations, we studied diverse gammabody-A¦Â recognition complexes to get insights into their structural and dynamic properties and gammabody-A¦Â recognitions. Among many heterogeneous binding modes, we focused on two gammabody-A¦Â recognition scenarios: recognition through A¦Â ¦Â-sheet backbone and on sidechain surface. We found that the gammabody primarily uses the complementarity-determining region 3 (CDR3) loop with the grafted A¦Â sequence to interact with the A¦Â fibril, while CDR1/CDR2 loops have very little contact. The gammabody-A¦Â complexes with backbone binding mode are more stable, explaining the gammabody¡¯s specificity towards the C-terminal A¦Â sequence. View Full-Tex
%K single-domain antibodies
%K A¦Â peptide
%K amyloid antibody
%K Alzheimer¡¯s disease
%K antibody recognition
%U https://www.mdpi.com/2073-4468/7/3/25