scholarly journals In SilicoIdentification of Potent PPAR-γAgonists from Traditional Chinese Medicine: A Bioactivity Prediction, Virtual Screening, and Molecular Dynamics Study

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Molecular Dynamics ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Virtual Screening ◽  
Prediction Models ◽  
Protein Complexes ◽  
Md Simulations ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
Key Residues

The peroxisome proliferator-activated receptors (PPARs) related to regulation of lipid metabolism, inflammation, cell proliferation, differentiation, and glucose homeostasis by controlling the related ligand-dependent transcription of networks of genes. They are used to be served as therapeutic targets against metabolic disorder, such as obesity, dyslipidemia, and diabetes; especially, PPAR-γis the most extensively investigated isoform for the treatment of dyslipidemic type 2 diabetes. In this study, we filter compounds of traditional Chinese medicine (TCM) using bioactivities predicted by three distinct prediction models before the virtual screening. For the top candidates, the molecular dynamics (MD) simulations were also utilized to investigate the stability of interactions between ligand and PPAR-γprotein. The top two TCM candidates, 5-hydroxy-L-tryptophan and abrine, have an indole ring and carboxyl group to form the H-bonds with the key residues of PPAR-γprotein, such as residues Ser289 and Lys367. The secondary amine group of abrine also stabilized an H-bond with residue Ser289. From the figures of root mean square fluctuations (RMSFs), the key residues were stabilized in protein complexes with 5-Hydroxy-L-tryptophan and abrine as control. Hence, we propose 5-hydroxy-L-tryptophan and abrine as potential lead compounds for further study in drug development process with the PPAR-γprotein.

scholarly journals Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Wang ◽  
Minghui Wan ◽  
Dongjiang Liao ◽  
Guilin Peng ◽  
Xin Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Natural Products ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Virtual Screening ◽  
Md Simulation ◽  
Interaction Analysis ◽  
Docking Simulation ◽  
Building Blocks ◽  
Intracellular Channel

Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition.

scholarly journals Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4094
Author(s):  
Yi Zhang ◽  
Ting-jian Zhang ◽  
Shun Tu ◽  
Zhen-hao Zhang ◽  
Fan-hao Meng
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Root Mean Square ◽  
Protein Complexes ◽  
Md Simulations ◽  
Binding Mode ◽  
Strong Interactions ◽  
Mean Square ◽  
Dynamics Simulations

Src plays a crucial role in many signaling pathways and contributes to a variety of cancers. Therefore, Src has long been considered an attractive drug target in oncology. However, the development of Src inhibitors with selectivity and novelty has been challenging. In the present study, pharmacophore-based virtual screening and molecular docking were carried out to identify potential Src inhibitors. A total of 891 molecules were obtained after pharmacophore-based virtual screening, and 10 molecules with high docking scores and strong interactions were selected as potential active molecules for further study. Absorption, distribution, metabolism, elimination and toxicity (ADMET) property evaluation was used to ascertain the drug-like properties of the obtained molecules. The proposed inhibitor–protein complexes were further subjected to molecular dynamics (MD) simulations involving root-mean-square deviation and root-mean-square fluctuation to explore the binding mode stability inside active pockets. Finally, two molecules (ZINC3214460 and ZINC1380384) were obtained as potential lead compounds against Src kinase. All these analyses provide a reference for the further development of novel Src inhibitors.

scholarly journals In Silico Screening and Analysis of Potential Inhibitors of Arylamine N-Acetyltransferases (NATs) from the Traditional Chinese Medicine: A Study Using Free Available Tools

2017 ◽  
Author(s):  
Francisco Azevedo ◽  
Joveline Richardt ◽  
Mayrla Oliveira ◽  
Inês Araujo ◽  
Ricardo Oliveira ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
In Silico ◽  
Md Simulations ◽  
Quality Information ◽  
Pharmacological Properties ◽  
Endogenous Compounds ◽  
Potential Inhibitors ◽  
Specific Ligand

Arylamine N-acetyltransferases (NATs) are cytosolic enzymes, highly polymorphic, present in both eukaryotes and prokaryotes. These enzymes play an important role in the detoxification and activation of xenobiotics as well as in the synthesis of endogenous compounds. Specific NATs have been pointed out in the literature as possible therapeutic targets. In particular, the human NAT1, for the treatment of certain cancers, and the NAT from M. tuberculosis (TBNAT), for the treatment of tuberculosis. This paper describes an in silico approach to prospect and select potentially inhibitors of NAT1 and TBNAT from the Traditional Chinese Medicine (TCM) using free available tools. A library with ligands from TCM was previously screened in order to select only compounds with optimal pharmacological properties. The affinity of the selected ligands with respect to NAT enzymes was then evaluated by virtual screening (VS). Subsequently, the complexes with the best ligands were submitted to molecular dynamics (MD) simulations aiming to obtain better quality information on affinity and selectivity. The results for one specific ligand, ZINC14690579, indicated its potential for affinity and selectivity. ZINC14690579 structure may represent the discovery of a new scaffold for future development of NAT inhibitors.

scholarly journals Virtual Screening for Potential Allosteric Inhibitors of Cyclin-Dependent Kinase 2 from Traditional Chinese Medicine

Molecules ◽  
2016 ◽  
Vol 21 (9) ◽  
pp. 1259 ◽  
Author(s):  
Fang Lu ◽  
Ganggang Luo ◽  
Liansheng Qiao ◽  
Ludi Jiang ◽  
Gongyu Li ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Virtual Screening ◽  
Cyclin Dependent Kinase ◽  
Allosteric Inhibitors

scholarly journals Molecular docking, pharmacophore based virtual screening and molecular dynamics studies towards the identification of potential leads for the management of H. pylori

RSC Advances ◽  
2019 ◽  
Vol 9 (45) ◽  
pp. 26176-26208 ◽  
Author(s):  
Manoj G. Damale ◽  
Rajesh B. Patil ◽  
Siddique Akber Ansari ◽  
Hamad M. Alkahtani ◽  
Abdulrahman A. Almehizia ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Md Simulations ◽  
Pharmacophore Modeling ◽  
Gastric Ulcers ◽  
Computational Approaches ◽  
Gastric Cancers ◽  
H Pylori

Computational approaches such as pharmacophore modeling, virtual screening and MD simulations were explored to find the potential hits as H. pylori specific panC inhibitors for the management of gastric ulcers and gastric cancers.

scholarly journals Investigation of Potent Lead for Acquired Immunodeficiency Syndrome from Traditional Chinese Medicine

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Tzu-Chieh Hung ◽  
Wen-Yuan Lee ◽  
Kuen-Bao Chen ◽  
Yueh-Chiu Chan ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Molecular Dynamics ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Acquired Immunodeficiency Syndrome ◽  
Hydrophobic Interactions ◽  
Structure Variation ◽  
Ligand Interactions ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Aurantiamide Acetate

Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), has become, because of the rapid spread of the disease, a serious global problem and cannot be treated. Recent studies indicate that VIF is a protein of HIV to prevent all of human immunity to attack HIV. Molecular compounds of traditional Chinese medicine (TCM) database filtered through molecular docking and molecular dynamics simulations to inhibit VIF can protect against HIV. Glutamic acid, plantagoguanidinic acid, and Aurantiamide acetate based docking score higher with other TCM compounds selected. Molecular dynamics are useful for analysis and detection ligand interactions. According to the docking position, hydrophobic interactions, hydrogen bonding changes, and structure variation, the study try to select the efficacy of traditional Chinese medicine compound Aurantiamide acetate is better than the other for protein-ligand interactions to maintain the protein composition, based on changes in the structure.

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