Computational analysis of De Novo evolution of Hepatitis C virus NS5B polymerase inhibitors

P. O.Yuan Chen; Wei Tse Hsu; Mien D.E. Jhuo; Che Yen Ou; Tzu-Hurng Cheng; Tzu Ching Shih; Chieh Hsi Wu; Rick Sai Chuan Wu; T. E.Chun Hsia; Jing Gung Chung

Computational analysis of De Novo evolution of Hepatitis C virus NS5B polymerase inhibitors

P. O.Yuan Chen, Wei Tse Hsu, Mien D.E. Jhuo, Che Yen Ou, Tzu-Hurng Cheng, Tzu Ching Shih, Chieh Hsi Wu, Rick Sai Chuan Wu, T. E.Chun Hsia, Jing Gung Chung

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear potential 1 (PLP1), piecewise linear potential 2 (PLP2), and potential of mean force (PMF) score of novel compounds. In this way, novel compounds with "de novo evolution" can be found. Using the the pharmacophore features that are near the receptor pocket and the score functions to calculate scores for the ligand-receptor interaction, the new ligands were selected, developed and virtually placed in the binding site of the receptor. A new compound, EVO12, gave the best score, indicating that it may be an efficient polymerase inhibitor of HCV NS5B.

Original language	English
Pages (from-to)	219-228
Number of pages	10
Journal	In Vivo
Volume	25
Issue number	2
Publication status	Published - 2011
Externally published	Yes

Keywords

Aromatic substituents
Computational analysis
HCV NS5B polymerase inhibitors

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
Pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

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title = "Computational analysis of De Novo evolution of Hepatitis C virus NS5B polymerase inhibitors",

abstract = "HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear potential 1 (PLP1), piecewise linear potential 2 (PLP2), and potential of mean force (PMF) score of novel compounds. In this way, novel compounds with {"}de novo evolution{"} can be found. Using the the pharmacophore features that are near the receptor pocket and the score functions to calculate scores for the ligand-receptor interaction, the new ligands were selected, developed and virtually placed in the binding site of the receptor. A new compound, EVO12, gave the best score, indicating that it may be an efficient polymerase inhibitor of HCV NS5B.",

keywords = "Aromatic substituents, Computational analysis, HCV NS5B polymerase inhibitors",

author = "Chen, {P. O.Yuan} and Hsu, {Wei Tse} and Jhuo, {Mien D.E.} and Ou, {Che Yen} and Tzu-Hurng Cheng and Shih, {Tzu Ching} and Wu, {Chieh Hsi} and Wu, {Rick Sai Chuan} and Hsia, {T. E.Chun} and Chung, {Jing Gung}",

year = "2011",

language = "English",

volume = "25",

pages = "219--228",

journal = "In Vivo",

issn = "0258-851X",

publisher = "International Institute of Anticancer Research",

number = "2",

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AU - Chen, P. O.Yuan

AU - Hsu, Wei Tse

AU - Jhuo, Mien D.E.

AU - Ou, Che Yen

AU - Cheng, Tzu-Hurng

AU - Shih, Tzu Ching

AU - Wu, Chieh Hsi

AU - Wu, Rick Sai Chuan

AU - Hsia, T. E.Chun

AU - Chung, Jing Gung

PY - 2011

Y1 - 2011

N2 - HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear potential 1 (PLP1), piecewise linear potential 2 (PLP2), and potential of mean force (PMF) score of novel compounds. In this way, novel compounds with "de novo evolution" can be found. Using the the pharmacophore features that are near the receptor pocket and the score functions to calculate scores for the ligand-receptor interaction, the new ligands were selected, developed and virtually placed in the binding site of the receptor. A new compound, EVO12, gave the best score, indicating that it may be an efficient polymerase inhibitor of HCV NS5B.

AB - HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear potential 1 (PLP1), piecewise linear potential 2 (PLP2), and potential of mean force (PMF) score of novel compounds. In this way, novel compounds with "de novo evolution" can be found. Using the the pharmacophore features that are near the receptor pocket and the score functions to calculate scores for the ligand-receptor interaction, the new ligands were selected, developed and virtually placed in the binding site of the receptor. A new compound, EVO12, gave the best score, indicating that it may be an efficient polymerase inhibitor of HCV NS5B.

KW - Aromatic substituents

KW - Computational analysis

KW - HCV NS5B polymerase inhibitors

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JO - In Vivo

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IS - 2

ER -

Computational analysis of De Novo evolution of Hepatitis C virus NS5B polymerase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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