Using reverse docking to identify potential targets for ginsenosides

Park, Kichul,Cho, Art E. The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.4

Background: Ginsenosides are the main ingredients of ginseng, which, in traditional Eastern medicine, has been claimed to have therapeutic values for many diseases. In order to verify the effects of ginseng that have been empirically observed, we utilized the reverse docking method to screen for target proteins that are linked to specific diseases. Methods: We constructed a target protein database including 1,078 proteins associated with various kinds of diseases, based on the Potential Drug Target Database, with an added list of kinase proteins. We screened 26 kinds of ginsenosides of this target protein database using docking. Results: We found four potential target proteins for ginsenosides, based on docking scores. Implications of these "hit" targets are discussed. From this screening, we also found four targets linked to possible side effects and toxicities, based on docking scores. Conclusion: Our method and results can be helpful for finding new targets and developing new drugs from natural products.

Using reverse docking to identify potential targets for ginsenosides

Kichul Park,Art E. Cho 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.4

Background: Ginsenosides are the main ingredients of ginseng, which, in traditional Eastern medicine, has been claimed to have therapeutic values for many diseases. In order to verify the effects of ginseng that have been empirically observed, we utilized the reverse docking method to screen for target proteins that are linked to specific diseases. Methods: We constructed a target protein database including 1,078 proteins associated with various kinds of diseases, based on the Potential Drug Target Database, with an added list of kinase proteins. We screened 26 kinds of ginsenosides of this target protein database using docking. Results: We found four potential target proteins for ginsenosides, based on docking scores. Implications of these “hit” targets are discussed. From this screening, we also found four targets linked to possible side effects and toxicities, based on docking scores. Conclusion: Our method and results can be helpful for finding new targets and developing new drugs from natural products.

Using reverse docking to identify potential targets for ginsenosides

박기철,조은성 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.4

Background: Ginsenosides are the main ingredients of ginseng, which, in traditional Eastern medicine, has been claimed to have therapeutic values for many diseases. In order to verify the effects of ginseng that have been empirically observed, we utilized the reverse docking method to screen for target proteins that are linked to specific diseases. Methods: We constructed a target protein database including 1,078 proteins associated with various kinds of diseases, based on the Potential Drug Target Database, with an added list of kinase proteins. We screened 26 kinds of ginsenosides of this target protein database using docking. Results: We found four potential target proteins for ginsenosides, based on docking scores. Implications of these “hit” targets are discussed. From this screening, we also found four targets linked to possible side effects and toxicities, based on docking scores. Conclusion: Our method and results can be helpful for finding new targets and developing new drugs from natural products.

Inferring B-cell derived T-cell receptor induced multi-epitope-based vaccine candidate against enterovirus 71: a reverse vaccinology approach

Swain Subrat Kumar,Panda Subhasmita,Sahu Basanta Pravas,Mahapatra Soumya Ranjan,Dey Jyotirmayee,Sarangi Rachita,Misra Namrata 대한백신학회 2024 Clinical and Experimental Vaccine Research Vol.13 No.2

Purpose: Enterovirus 71, a pathogen that causes hand-foot and mouth disease (HFMD) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in pediatric patients with blister-like sores or rashes on the hand, feet, and mouth. Notwithstanding the significant burden of the disease, no authorized vaccine is available. Previously identified attenuated and inactivated vaccines are worthless over time owing to changes in the viral genome. Materials and Methods: A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein found the induction of possible immune response. In order to boost the immune system, a beta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence. Results: The immunogenicity of the designed, refined, and verified prospective threedimensional-structure of the multi-epitope vaccine was found to be quite high, exhibiting nonallergenic and antigenic properties. The vaccine candidates bound to toll-like receptor 3 in a molecular docking analysis, and the efficacy of the potential vaccine to generate a strong immune response was assessed through in silico immunological simulation. Conclusion: Computational analysis has shown that the proposed multi-epitope vaccine is possibly safe for use in humans and can elicit an immune response.

Comparative Reverse Screening Approach to Identify Potential Anti-neoplastic Targets of Saffron Functional Components and Binding Mode

Bhattacharjee, Biplab,Vijayasarathy, Sandhya,Karunakar, Prashantha,Chatterjee, Jhinuk Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Background: In the last two decades, pioneering research on anti-tumour activity of saffron has shed light on the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exact mechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituents will play an imperative role in demystifying the complex anti-neoplastic machinery. Methods: In the quest of potential target identification, a dual virtual screening approach utilizing two inverse screening systems, one predicated on idTarget and the other on PharmMapper was here employed. A set of target proteins associated with multiple forms of cancer and ranked by Fit Score and Binding energy were obtained from the two independent inverse screening platforms. The validity of the results was checked by meticulously analyzing the post-docking binding pose of the picrocrocin with Hsp90 alpha in AutoDock. Results: The docking pose reveals that electrostatic and hydrogen bonds play the key role in inter-molecular interactions in ligand binding. Picrocrocin binds to the Hsp90 alpha with a definite orientation appropriate for nucleophilic attacks by several electrical residues inside the Hsp90-alpha ATPase catalytic site. Conclusion: This study reveals functional information about the anti-tumor mechanism of saffron bioactive constituents. Also, a tractable set of anti-neoplastic targets for saffron has been generated in this study which can be further authenticated by in vivo and in vitro experiments.

Inhibitions of monoamine oxidases by ferulic acid hydrazide derivatives: synthesis, biochemistry, and computational evaluation

Peedikayil Arshida Thottile,Lee Jiseong,Abdelgawad Mohamed A.,Ghoneim Mohammed M.,Shaker Mohamed E.,Selim Samy,Kumar Sunil,Dev Sanal,Kim Hoon,Mathew Bijo 한국응용생명화학회 2023 Applied Biological Chemistry (Appl Biol Chem) Vol.66 No.-

Monoamine oxidases (MAOs) regulate neurotransmitters, and changes in their regulation lead to neurogenerative diseases (NDs). Therefore, MAO inhibitors are used to treat NDs. Ferulic acid, a phenolic compound found in various plant species, has been demonstrated to have a variety of biological functions, including anti-inflammatory, anticancer, and neuroprotective effects. In this study, ten ferulic acid hydrazide derivatives (FA1–FA10) were synthesized, and their ability to inhibit monoamine oxidase (MAO) enzymes was tested. Six candidates demonstrated a more pronounced pattern of inhibitory action against MAO-B than against MAO-A. FA3 had the highest inhibitory efficacy in MAO-B inhibition (IC50 value of 1.88 μM), followed by FA9 (2.08 μM). FA3 has a Ki of 1.92 ± 0.73 μM. A reversibility experiment of MAO-B inhibition by FA3 was conducted using dialysis, and the recovery pattern showed FA3 was a reversible MAO-B inhibitor with a similar recovery to safinamide, a reversible reference inhibitor. These results indicate that FA3 is an effective reversible MAO-B inhibitor. In molecular dynamics and docking, FA3 paired with pi-pi stacking helped stabilize the protein ligand in the active site of MAO-B. According to this study, lead compounds can be used as therapeutic agents to treat neurological conditions, such as Parkinson's disease (PD).

Pannorin isolated from marine Penicillium sp. SG-W3: a selective monoamine oxidase A inhibitor

Oh Jong Min,Gao Qian,Shin Woong-Hee,Lee Eun-Young,Chung Dawoon,Choi Grace,Nam Sang-Jip,Kim Hoon 한국응용생명화학회 2024 Applied Biological Chemistry (Appl Biol Chem) Vol.67 No.-

Six compounds were isolated from Penicillium sp. SG-W3, a marine-derived fungus, and their inhibitory activities against target enzymes relating to neurological diseases were evaluated. Compound 1 (pannorin) was a potent and selective monoamine oxidase (MAO)-A inhibitor with a 50% inhibitory concentration ( IC50) of 1.734 μM and a selectivity index (SI) of > 23.07 versus MAO-B, and it showed an efficient antioxidant activity. All compounds showed weak inhibitory activities against acetylcholinesterase, butyrylcholinesterase, and β-secretase. The inhibition constant ( Ki) of 1 for MAO-A was 1.049 ± 0.030 μM with competitive inhibition. Molecular docking simulation predicted that compound 1 forms hydrogen bonds with MAO-A, and binds more tightly to MAO-A than to MAO-B (− 25.02 and − 24.06 kcal/mol, respectively). These results suggest that compound 1 is a selective, reversible, and competitive MAO-A inhibitor that can be a therapeutic candidate for treating neurological diseases.