TY - JOUR
T1 - Interaction of antivirals with a heptameric bundle model of the p7 protein of hepatitis C virus
AU - Dahl, Sophie L.
AU - Kalita, Monoj Mon
AU - Fischer, Wolfgang B.
N1 - Publisher Copyright:
© 2017 John Wiley & Sons A/S
PY - 2018/4
Y1 - 2018/4
N2 - A series of ligands are known experimentally to affect the infectivity cycle of the hepatitis C virus. The target protein for the ligands is proposed to be p7, a 63 amino acid polytopic channel-forming protein, with possibly two transmembrane domains. Protein p7 is found to assemble into functional oligomers of various sizes, depending on the genotype (GT). Nine ligands are docked to various sites of a computationally derived heptameric bundle of p7 of GT1a. The energy of interaction, here binding energy, is calculated using three different docking programs (Autodock, MOE, LeadIT). Three protein regions are defined to which the ligands are placed, the loop region and the site with the termini as well as the mid-region which is supposed to track poses inside the putative pore. A common feature is that the loop sites and poses either within the pore or at the intermonomer space of the bundle are preferred for all ligands with proposed binding energies smaller than −10 kJ/mol. BIT225, benzamine, amantadine, and NN-DNJ show good overall scoring.
AB - A series of ligands are known experimentally to affect the infectivity cycle of the hepatitis C virus. The target protein for the ligands is proposed to be p7, a 63 amino acid polytopic channel-forming protein, with possibly two transmembrane domains. Protein p7 is found to assemble into functional oligomers of various sizes, depending on the genotype (GT). Nine ligands are docked to various sites of a computationally derived heptameric bundle of p7 of GT1a. The energy of interaction, here binding energy, is calculated using three different docking programs (Autodock, MOE, LeadIT). Three protein regions are defined to which the ligands are placed, the loop region and the site with the termini as well as the mid-region which is supposed to track poses inside the putative pore. A common feature is that the loop sites and poses either within the pore or at the intermonomer space of the bundle are preferred for all ligands with proposed binding energies smaller than −10 kJ/mol. BIT225, benzamine, amantadine, and NN-DNJ show good overall scoring.
KW - adamantanes
KW - guanidinium compounds
KW - imino-sugars
KW - p7 of HCV
KW - viral channel protein
UR - http://www.scopus.com/inward/record.url?scp=85040796002&partnerID=8YFLogxK
U2 - 10.1111/cbdd.13162
DO - 10.1111/cbdd.13162
M3 - Article
C2 - 29251816
AN - SCOPUS:85040796002
SN - 1747-0277
VL - 91
SP - 942
EP - 950
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
IS - 4
ER -