TY - JOUR
T1 - Assessment of Drug Binding Potential of Pockets in the NS2B/NS3 Dengue Virus Protein
AU - Amelia, F.
AU - Iryani,
AU - Sari, P. Y.
AU - Parikesit, A. A.
AU - Bakri, R.
AU - Toepak, E. P.
AU - Tambunan, U. S.F.
N1 - Funding Information:
We thank the Indonesian government for funding this research, Hibah Pekerti – DIKTI No: 237/UN35.2/PG/2015 and Hibah Penelitian Unggulan Perguruan Tinggi (PUPT) 2017 No: 2716/UN2.R3.1/HKP.05.00/2017. In this research; Usman Sumo Friend Tambunan, Arli Aditya Parikesit, Ridla Bakri and Fitri Amelia were supervising the research. Iryani and Prima Yulia Sari conducted the experiments, while Erwin Prasetya Toepak helped to proofread the paper
Publisher Copyright:
© 2018 Institute of Physics Publishing. All rights reserved.
PY - 2018/5/2
Y1 - 2018/5/2
N2 - Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å 3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.
AB - Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å 3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.
UR - http://www.scopus.com/inward/record.url?scp=85047738261&partnerID=8YFLogxK
U2 - 10.1088/1757-899X/349/1/012021
DO - 10.1088/1757-899X/349/1/012021
M3 - Conference article
AN - SCOPUS:85047738261
SN - 1757-8981
VL - 349
JO - IOP Conference Series: Materials Science and Engineering
JF - IOP Conference Series: Materials Science and Engineering
IS - 1
M1 - 012021
T2 - 12th Joint Conference on Chemistry, JCC 2017
Y2 - 19 September 2017 through 20 September 2017
ER -