Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method

Abstract

The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs. Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus. To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique. As a result, the Neo6 compound was obtained. It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor. Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza. Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area.

Computational analyses on delineating specificity of 2-hydroxy-3,5-dinitrobenzamide, a BH3-mimetic, towards anti-apoptotic proteins

“…In other words, the two nitro groups did not make any essential non-bonding interactions with other 4 anti-apoptotic proteins (Bcl-B, Bcl-XL, Bfl-1 and Mcl-1). In these backgrounds, structural determinants identified for the HDNB and as well for anti-apoptotic proteins for generating protein-ligand complexes may pave ways for developing highly efficient and specific prototype molecules to each of the anti-apoptotic proteins using HDNB as seed molecule by means of 'core hopping' (Li et al, 2011) and 'de novo' drug designing strategies in near future.…”

pLoc-mGpos: Incorporate Key Gene Ontology Information into General PseAAC for Predicting Subcellular Localization of Gram-Positive Bacterial Proteins

“…incorrectly predicted to be of the i-th location. The metrics of Equation (19) have been widely used to examine the quality of predictors in genome/proteome analysis (see, e.g., [46,47,[76][77][78][79][80][107][108][109]) and computational biomedicine (see, e.g., [82,[110][111][112]). Natural Science Given in Table 3 are the corresponding results obtained by pLoc-mGpos for each of the four subcellular locations.…”

“…With more experimental data emerging, however, the localization of proteins in a cell is actually a multi-label system, where some proteins may simultaneously occur in two or more different location sites. This kind of multiplex proteins often bears some exceptional biological functions [4][5][6], and should deserve our special attention [7][8][9][10][11][12], particularly from the viewpoint of selecting multiple targets [13][14][15] or key targets [16][17][18][19] for drug development.…”

Molecular Recognition of Human Angiotensin-Coverting Enzyme I (hACE I) and Different Inhibitors

“…Such a criterion was originally used to define the binding pocket of ATP in the Cdk5-Nck5a* complex [61] that has later proved quite useful in identifying functional domains and stimulating the relevant truncation experiments [62]. The similar approach has also been used to define the binding pockets of many other receptor-ligand interactions important for drug design [63][64][65][66][67][68][69][70][71][72][73][74].…”