TY - JOUR
T1 - Designing of disulfide cyclic peptide for inhibiting polymerase A and B1 (PAC-PB1N) in H1N1 virus using molecular simulation approach
AU - Friend, Usman Sumo
AU - Nasution, Mochammad Arfin Fardiansyah
AU - Parikesit, Arli Aditya
AU - Noviardi, Harry
AU - Kirani, Djati
N1 - Publisher Copyright:
© 2016 Usman Sumo Friend Tambunan, Mochammad Arfin Fardiansyah Nasution, Arli Aditya Parikesit, Harry Noviardi and Djati Kerami.
PY - 2016
Y1 - 2016
N2 - The drug resistance A/H1N1 flu virus is emerging rapidly. Therefore, looking for potential therapy is very important. PB2, PB and PA are subunits of viral RNA-dependent RNA polymerase (RdRp). They play an important role in viral replication. The PA and PB1 binding sites can be considered as potential targets for the development of new influenza drugs. The peptide inhibitors can be designed specifically due to their highpreferred activity. In this study, the cyclic peptide ligands were designed based on the crystal structure of PAC-PB1Nin the surface of the molecule, resulting 1728 cyclopentadienyl compounds. The MOE 2008.10 software was utilized for molecular docking and dynamics simulation approach, while Lipinski’s Rules of Five were utilized to evaluate the feasibility of drug candidates. Thus, molecular dynamics simulation was applied, in order to facilitate the interaction between the ligand and enzyme. The simulations have successfully produced two cyclopentyl peptides, namely CKKTC and CKTTC, which results in both ligands providing a potent inhibitor of polymerase PAC-PB1Nof Influenza A/2009 (H1N1).
AB - The drug resistance A/H1N1 flu virus is emerging rapidly. Therefore, looking for potential therapy is very important. PB2, PB and PA are subunits of viral RNA-dependent RNA polymerase (RdRp). They play an important role in viral replication. The PA and PB1 binding sites can be considered as potential targets for the development of new influenza drugs. The peptide inhibitors can be designed specifically due to their highpreferred activity. In this study, the cyclic peptide ligands were designed based on the crystal structure of PAC-PB1Nin the surface of the molecule, resulting 1728 cyclopentadienyl compounds. The MOE 2008.10 software was utilized for molecular docking and dynamics simulation approach, while Lipinski’s Rules of Five were utilized to evaluate the feasibility of drug candidates. Thus, molecular dynamics simulation was applied, in order to facilitate the interaction between the ligand and enzyme. The simulations have successfully produced two cyclopentyl peptides, namely CKKTC and CKTTC, which results in both ligands providing a potent inhibitor of polymerase PAC-PB1Nof Influenza A/2009 (H1N1).
KW - Five-ring peptides
KW - Influenza A
KW - Molecular docking
KW - Molecular dynamics
KW - Polymerase PA-PB1
UR - http://www.scopus.com/inward/record.url?scp=84994607963&partnerID=8YFLogxK
U2 - 10.3844/ojbsci.2016.122.129
DO - 10.3844/ojbsci.2016.122.129
M3 - Article
AN - SCOPUS:84994607963
SN - 1608-4217
VL - 16
SP - 122
EP - 129
JO - OnLine Journal of Biological Sciences
JF - OnLine Journal of Biological Sciences
IS - 3
ER -