ABSTRACT
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.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Antiviral Agents/chemistry , Medicine, Chinese Traditional , Viral Proteins/chemistry , Acquired Immunodeficiency Syndrome/pathology , Acquired Immunodeficiency Syndrome/virology , Antiviral Agents/therapeutic use , HIV/drug effects , Humans , Hydrogen Bonding/drug effects , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Viral Proteins/antagonists & inhibitorsABSTRACT
Human immunodeficiency virus causes the acquired immunodeficiency syndrome (AIDS) and becomes a serious world-wide problem because of this disease's rapid propagation and incurability. Integrase strand transfer inhibitors (INSTIs) supports HIV have rapid drug resistance for antitreatment. Screening the traditional Chinese medicine (TCM) database by simulating molecular docking and molecular dynamics may select molecular compounds to inhibit INSTIs against HIV drug resistance. (S)-cathinone and (1S,2S)-norpseudoephedrine are selected based on structure and ligand-based drugs are designed and then get higher bioactivity predicted score from SVM than Raltegravir and other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions and hydrogen bond variations define the main regions of important amino acids in integrase. In addition to the detection of TCM compound efficacy, we suggest (1S,2S)-norpseudoephedrine is better than the others based on the analysis of interaction and the effect on the structural variation.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Enzyme Inhibitors/therapeutic use , HIV Integrase/chemistry , HIV/drug effects , Acquired Immunodeficiency Syndrome/virology , Databases, Factual , Drug Evaluation, Preclinical , Enzyme Inhibitors/chemistry , HIV Integrase/drug effects , Humans , Medicine, Chinese Traditional , Molecular Dynamics SimulationABSTRACT
Recently, an important topic of breast cancer had been published in 2013. In this report, estrogen receptor (ESR1) had defined the relation of hormone-cause breast cancer. The screening of traditional Chinese medicine (TCM) database has found the molecular compounds by simulating molecular docking and molecular dynamics to regulate ESR1. S-Allylmercaptocysteine and 5-hydroxy-L-tryptophan are selected according to the highest docking score than that of other TCM compounds and Raloxifene (control). The simulation from molecular dynamics is helpful in analyzing and detecting the protein-ligand interactions. After a comparing the control and the Apo form, then based on the docking poses, hydrophobic interactions, hydrogen bond and structure variations, this research postulates that S-allylmercaptocysteine may be more appropriate than other compounds for protein-ligand interaction.
Subject(s)
Breast Neoplasms/drug therapy , Estrogen Receptor alpha/chemistry , Medicine, Chinese Traditional , 5-Hydroxytryptophan/chemistry , Binding Sites , Computational Biology , Computer Simulation , Crystallography, X-Ray , Cysteine/analogs & derivatives , Cysteine/chemistry , Databases, Factual , Drug Design , Female , Humans , Ligands , Molecular Docking Simulation , Protein Binding , Protein Conformation , Proteins/chemistryABSTRACT
Recently, an important topic of liver tumorigenesis had been published in 2013. In this report, Ras and Rho had defined the relation of liver tumorigenesis. The traditional Chinese medicine (TCM) database has been screened for molecular compounds by simulating molecular docking and molecular dynamics to regulate Ras and liver tumorigenesis. Saussureamine C, S-allylmercaptocysteine, and Tryptophan are selected based on the highest docking score than other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. Based on the docking poses, hydrophobic interactions, and hydrogen bond variations, this research surmises are the main regions of important amino acids in Ras. In addition to the detection of TCM compound efficacy, we suggest Saussureamine C is better than the others for protein-ligand interaction.
Subject(s)
Carcinogenesis/genetics , Liver Neoplasms/genetics , Medicine, Chinese Traditional , Monomeric GTP-Binding Proteins/genetics , Binding Sites , Humans , Hydrogen Bonding , Ligands , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Molecular Docking Simulation , Molecular Dynamics Simulation , Monomeric GTP-Binding Proteins/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , rho-Associated Kinases/geneticsABSTRACT
Recently, an important topic of major depressive disorder (MDD) had been published in 2013. MDD is one of the most prevalent and disabling mental disorders. Consequently, much research is being undertaken into the causes and treatment. It has been found that inhibition of the ß form of calcium/calmodulin-dependent protein kinase type II (ß-CaMKII) can ameliorate the disorder. Upon screening the traditional Chinese medicine (TCM) database by molecular docking, sengesterone, labiatic acid, and methyl 3-O-feruloylquinate were selected for molecular dynamics. After 20 ns simulation, the RMSD, total energy, and structure variation could define the protein-ligand interaction. Furthermore, sengesterone, the principle candidate compound, has been found to have an effect on the regulation of emotions and memory development. In structure variation, we find the sample functional group of important amino acids make the protein stable and have limited variation. Due to similarity of structure variations, we suggest that these compounds may have an effect on ß-CaMKII and that sengesterone may have a similar efficacy as the control. However labiatic acid may be a stronger inhibitor of ß-CaMKII based on the larger RMSD and variation.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/chemistry , Depressive Disorder, Major/drug therapy , Enzyme Inhibitors/chemistry , Medicine, Chinese Traditional , Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Depressive Disorder, Major/pathology , Drug Design , Enzyme Inhibitors/therapeutic use , Humans , Ligands , Molecular Docking Simulation , Molecular Dynamics SimulationABSTRACT
Human histone deacetylase 2 (HDAC2) has been identified as being associated with Alzheimer's disease (AD), a neuropathic degenerative disease. In this study, we screen the world's largest Traditional Chinese Medicine (TCM) database for natural compounds that may be useful as lead compounds in the search for inhibitors of HDAC2 function. The technique of molecular docking was employed to select the ten top TCM candidates. We used three prediction models, multiple linear regression (MLR), support vector machine (SVM), and the Bayes network toolbox (BNT), to predict the bioactivity of the TCM candidates. Molecular dynamics simulation provides the protein-ligand interactions of compounds. The bioactivity predictions of pIC50 values suggest that the TCM candidatesm, (-)-Bontl ferulate, monomethylcurcumin, and ningposides C, have a greater effect on HDAC2 inhibition. The structure variation caused by the hydrogen bonds and hydrophobic interactions between protein-ligand interactions indicates that these compounds have an inhibitory effect on the protein.
Subject(s)
Alzheimer Disease/drug therapy , Enzyme Inhibitors/administration & dosage , Histone Deacetylase 2/antagonists & inhibitors , Medicine, Chinese Traditional , Alzheimer Disease/pathology , Computer Simulation , Enzyme Inhibitors/chemistry , Humans , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Quantitative Structure-Activity Relationship , Support Vector MachineABSTRACT
Recently, an important topic of the acquired immunodeficiency syndrome (AIDS) had been published in 2013. In this report, the expression of the IFN-induced myxovirus resistance 2 (MX2) had been defined the function to kill the human immunodeficiency virus (HIV). The screening from the Traditional Chinese Medicine (TCM) database by simulating molecular docking and molecular dynamics could select candidate compounds, which may express MX2 against HIV. Saussureamine C, Crotalaburnine, and Precatorine are selected based on the highest docking score and other TCM compounds. The data from molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions, and hydrogen bond with structure variations, this research could assess the interaction between protein and ligand interaction. In addition to the detection of TCM compound efficacy, we suggest that Saussureamine C is better than the others in protein-ligand interaction and the structural variation to express MX2.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Drugs, Chinese Herbal/chemistry , Medicine, Chinese Traditional , Myxovirus Resistance Proteins/biosynthesis , Acquired Immunodeficiency Syndrome/genetics , Acquired Immunodeficiency Syndrome/virology , Asparagine/analogs & derivatives , Asparagine/chemistry , Asparagine/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Gene Expression Regulation/drug effects , HIV/drug effects , HIV/genetics , Humans , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Myxovirus Resistance Proteins/antagonists & inhibitors , Pyrrolizidine Alkaloids/chemistry , Pyrrolizidine Alkaloids/therapeutic use , Tryptophan/analogs & derivatives , Tryptophan/chemistry , Tryptophan/therapeutic useABSTRACT
Insomnia is a prominent modern disease that affects an increasing population. Undesirable side effects of commercial drugs highlight the need to develop novel insomnia drugs. Virtual screening of traditional chinese medicine Database@Taiwan (TCM Database@Taiwan) identified 2-O-Caffeoyl tartaric acid (1), 2-O-Feruloyl tartaric acid (2), and Mumefural (3) as potential agonists for both gamma-amino butyric acid (GABA) or benzodiazepine (BZ) binding sites. The TCM candidates exhibited higher affinity than GABA and Zolpidem, a phenomenon that could be attributed to higher quantity of stabilizing H-bonds. Efficacy profiles using support vector machines and pharmacophore contour also suggest drug potential of the TCM candidates. Fragments added to the de novo derivatives 3a, 3b, 3c for GABA binding site, and 1a, 2a, and 3d for BZ binding site contributed to new binding sites and structural stability, further optimizing binding to GABA or BZ binding sites. Increased opening of the ion channel by candidate ligands provide strong support for their potential biological functions. The dual binding properties of the TCM candidates present a unique opportunity to develop twin-targeting drugs with less side effects. Derivative structures can be used as starting points for developing high affinity GABAA receptor agonists with specificity towards GABA binding site and BZ binding site.