Computational Design of Dengue Type-2 NS2B/NS3 Protease Inhibitor: 2D/3D QSAR of Quinoline and Its Molecular Docking

DOI

10.2991/iccst-15.2015.13How to use a DOI?

Keywords

DENV2 NS2B/NS3 protease, genetic function approximation, molecular docking, qsar, quinoline

Abstract

The reemergence of dengue outbreak demands an effective and efficient treatment especially for antiviral agent since neither vaccine nor drug is available to overcome this disease. This study designed the new model for Dengue Type-2 (DENV2) NS2B/NS3 protease inhibitor from quinoline scaffold by combining QSAR modeling with molecular docking. Genetic Function Approximation (GFA) method was used to construct the QSAR model showing good correlation coefficient (r2 = 0.8996). The model was validated using Partial Least Square (PLS) analysis (r2 = 0.861), Leave One Out - Cross Validation (LOO-CV with q2 = 0.677) and external validation (r2 = 0.854). The model was then used to design more quinoline derivatives by attaching more electron withdrawing group such as halogen and aldehyde. Ssearching for more diverse structure of protease inhibitors was carried out by screening out NCI database. Results showed that the QSAR model was able to predict the new protease inhibitor model with a nanomolar inhibition. The molecular docking was then performed to predict the binding mode of all protease inhibitor models and revealed that most of essential amino acid residues such as Ile36, His51, Ser135, Asp129, Tyr150, Gly151, Gly153 and Val154 significantly interact with the ligands. Based on the agreement between QSAR modeling and molecular docking results, the designed molecules were reported gaining insight activities as DENV2 NS2B/NS3 protease inhibitor.

Copyright

© 2015, the Authors. Published by Atlantis Press.

Open Access

This is an open access article distributed under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - CONF
AU  - Maywan Hariono
AU  - Ezatul E. Kamarulzaman
AU  - Habibah Wahab
PY  - 2015/01
DA  - 2015/01
TI  - Computational Design of Dengue Type-2 NS2B/NS3 Protease Inhibitor: 2D/3D QSAR of Quinoline and Its Molecular Docking
BT  - Proceedings of the 3rd International Conference on Computation for Science and Technology
PB  - Atlantis Press
SP  - 63
EP  - 81
SN  - 2352-538X
UR  - https://doi.org/10.2991/iccst-15.2015.13
DO  - 10.2991/iccst-15.2015.13
ID  - Hariono2015/01
ER  -