scholarly journals An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings

2017 ◽  
Author(s):  
Irene Maffucci ◽  
Xiao Hu ◽  
Valentina Fumagalli ◽  
Alessandro Contini
Keyword(s):  
Binding Energy ◽  
Virtual Screening ◽  
Md Simulation ◽  
Protein Complexes ◽  
Efficient Implementation ◽  
Water Molecules ◽  
Contact Interface ◽  
Experimental Binding Energy ◽  
Selection Of

The Nwat-MMGBSA method, whose theory has been described in Maffucci & Contini, JCTC 2013, 9, 2706, is based on the inclusion as part of the receptor of a given number of water molecules (Nwat) which are the closest to a residue (generally the ligand) or to a selection of residues (the contact interface) in each frame of the MD simulation. The method was shown to improve the correlation between predicted and experimental binding energy in both ligand-receptor and protein-protein complexes (Maffucci & Contini, JCIM 2016, 56, 1692). Here, we report on the optimization of the Nwat-MMGBSA protocol for its use to rescore docking results. We also report an automatic workflow, based on three independent scripts (which can be concatenated in a fully automated procedure) to easily employ Nwat-MMGBSA rescoring in virtual screening application. The protocol has been tuned using three different examples, and then tested in two retrospective virtual screening examples. In each example, the Nwat-MMGBSA method has been compared with the standard MMGBSA approach (Nwat=0). A link to download the scripts, working examples and tutorials is also provided.<br><br>

scholarly journals An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings

2017 ◽  
Author(s):  
Irene Maffucci ◽  
Xiao Hu ◽  
Valentina Fumagalli ◽  
Alessandro Contini
Keyword(s):  
Binding Energy ◽  
Virtual Screening ◽  
Md Simulation ◽  
Protein Complexes ◽  
Efficient Implementation ◽  
Water Molecules ◽  
Contact Interface ◽  
Experimental Binding Energy ◽  
Selection Of

The Nwat-MMGBSA method, whose theory has been described in Maffucci & Contini, JCTC 2013, 9, 2706, is based on the inclusion as part of the receptor of a given number of water molecules (Nwat) which are the closest to a residue (generally the ligand) or to a selection of residues (the contact interface) in each frame of the MD simulation. The method was shown to improve the correlation between predicted and experimental binding energy in both ligand-receptor and protein-protein complexes (Maffucci & Contini, JCIM 2016, 56, 1692). Here, we report on the optimization of the Nwat-MMGBSA protocol for its use to rescore docking results. We also report an automatic workflow, based on three independent scripts (which can be concatenated in a fully automated procedure) to easily employ Nwat-MMGBSA rescoring in virtual screening application. The protocol has been tuned using three different examples, and then tested in two retrospective virtual screening examples. In each example, the Nwat-MMGBSA method has been compared with the standard MMGBSA approach (Nwat=0). A link to download the scripts, working examples and tutorials is also provided.<br><br>

Screening of Anti-mycobacterial Phytochemical Compounds for Potential Inhibitors against Mycobacterium Tuberculosis Isocitrate Lyase

2019 ◽  
Vol 19 (8) ◽  
pp. 600-608 ◽  
Author(s):  
Ashish Tiwari ◽  
Akhil Kumar ◽  
Gaurava Srivastava ◽  
Ashok Sharma
Keyword(s):  
Binding Energy ◽  
Virtual Screening ◽  
Md Simulation ◽  
Isocitrate Lyase ◽  
Docking Study ◽  
High Morbidity ◽  
Average Binding Energy ◽  
Ic50 Value ◽  
Key Enzyme ◽  
Potential Inhibitors

Conclusion:Phytochemical based anti-mycobacterial compound can further developed into effective drugs against persistence tuberculosis with lesser toxicity and side effects.Results:Docking and MD simulation studies of top hit compounds have identified shinjudilactone (quassinoid), lecheronol A (pimarane) and caniojane (diterpene) as potential MtbICL inhibitors.Methods:Virtual screening, molecular docking and MD simulation study has been integrated for screening of phytochemical based anti-mycobacterial compounds. Docking study of reported MtbICL inhibitors has shown an average binding affinity score -7.30 Kcal/mol. In virtual screening, compounds exhibiting lower binding energy than calculated average binding energy were selected as top hit compounds followed by calculation of drug likeness property. Relationship between experimental IC50 value and calculated binding gibbs free energy of reported inhibitors was also calculated through regression analysis to predict IC50 value of potential inhibitors.Background and Introduction:Tuberculosis (TB) is a leading infectious disease caused by Mycobacterium tuberculosiswith high morbidity and mortality. Isocitrate lyase (MtbICL), a key enzyme of glyoxylate pathway has been shown to be involved in mycobacterial persistence, is attractive drug target against persistent tuberculosis.

Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach

2018 ◽  
Vol 15 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Md. Mostafijur Rahman ◽  
Md. Bayejid Hosen ◽  
M. Zakir Hossain Howlader ◽  
Yearul Kabir
Keyword(s):  
Binding Energy ◽  
Middle East ◽  
Virtual Screening ◽  
In Silico ◽  
Screening Method ◽  
Middle East Respiratory Syndrome ◽  
Cytochrome P450 Enzymes ◽  
Drug Molecules ◽  
Essential Enzyme ◽  
Reduced Toxicity

Background: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. </P><P> Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. Results: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

scholarly journals An Overview of Molecular Dynamic Simulation for Corrosion Inhibition of Ferrous Metals

Metals ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 46
Author(s):  
Nur Izzah Nabilah Haris ◽  
Shafreeza Sobri ◽  
Yus Aniza Yusof ◽  
Nur Kartinee Kassim
Keyword(s):  
Molecular Dynamic ◽  
Corrosion Inhibition ◽  
High Performance ◽  
Md Simulation ◽  
Ferrous Metal ◽  
Working Mechanism ◽  
Inhibitor Molecule ◽  
As Adsorption ◽  
Inhibition Studies ◽  
Selection Of

Molecular dynamics (MD) simulation is a powerful tool to study the molecular level working mechanism of corrosion inhibitors in mitigating corrosion. In the past decades, MD simulation has emerged as an instrument to investigate the interactions at the interface between the inhibitor molecule and the metal surface. Combined with experimental measurement, theoretical examination from MD simulation delivers useful information on the adsorption ability and orientation of the molecule on the surface. It relates the microscopic characteristics to the macroscopic properties which enables researchers to develop high performance inhibitors. Although there has been vast growth in the number of studies that use molecular dynamic evaluation, there is still lack of comprehensive review specifically for corrosion inhibition of organic inhibitors on ferrous metal in acidic solution. Much uncertainty still exists on the approaches and steps in performing MD simulation for corrosion system. This paper reviews the basic principle of MD simulation along with methods, selection of parameters, expected result such as adsorption energy, binding energy and inhibitor orientation, and recent publications in corrosion inhibition studies.

scholarly journals Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Firoz A. Dain Md Opo ◽  
Mohammed M. Rahman ◽  
Foysal Ahammad ◽  
Istiak Ahmed ◽  
Mohiuddin Ahmed Bhuiyan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Md Simulation ◽  
Pharmacophore Model ◽  
Pharmacophore Modeling ◽  
Drug Candidate ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Apoptosis Process

AbstractX-linked inhibitor of apoptosis protein (XIAP) is a member of inhibitor of apoptosis protein (IAP) family responsible for neutralizing the caspases-3, caspases-7, and caspases-9. Overexpression of the protein decreased the apoptosis process in the cell and resulting development of cancer. Different types of XIAP antagonists are generally used to repair the defective apoptosis process that can eliminate carcinoma from living bodies. The chemically synthesis compounds discovered till now as XIAP inhibitors exhibiting side effects, which is making difficulties during the treatment of chemotherapy. So, the study has design to identifying new natural compounds that are able to induce apoptosis by freeing up caspases and will be low toxic. To identify natural compound, a structure-based pharmacophore model to the protein active site cavity was generated following by virtual screening, molecular docking and molecular dynamics (MD) simulation. Initially, seven hit compounds were retrieved and based on molecular docking approach four compounds has chosen for further evaluation. To confirm stability of the selected drug candidate to the target protein the MD simulation approach were employed, which confirmed stability of the three compounds. Based on the finding, three newly obtained compounds namely Caucasicoside A (ZINC77257307), Polygalaxanthone III (ZINC247950187), and MCULE-9896837409 (ZINC107434573) may serve as lead compounds to fight against the treatment of XIAP related cancer, although further evaluation through wet lab is necessary to measure the efficacy of the compounds.

scholarly journals VIRTUAL SCREENING OF BETA-SECRETASE 1 (BACE1) INHIBITORS IN THE INDONESIAN HERBAL DATABASE AS USING AUTODOCK AND AUTODOCK VINA

2017 ◽  
Vol 10 (17) ◽  
pp. 148
Author(s):  
Asti Anna Tanisa ◽  
Rezi Riadhi
Keyword(s):  
Binding Energy ◽  
Virtual Screening ◽  
Cellular Response ◽  
Senile Plaque ◽  
Area Under The Curve ◽  
Neuronal System ◽  
Operating Characteristics ◽  
Autodock Vina ◽  
Beta Secretase ◽  
The Brain

  Objective: Alzheimer’s is a neurodegenerative disease caused by the accumulation of senile plaque in the brain that affects neuronal system leading to a less sensitive cellular response from neurons. Previous research has found that beta-secretase 1 (BACE1) plays an important role in the senile plaque formation, become a target in Alzheimer’s medication.Methods: In this study, virtual screening of BACE1 inhibitors on the Indonesian Herbal Database was done using AutoDock and AutoDock Vina. The screening was validated using the directory of useful decoys: Enhanced database. Parameters for validation process of AutoDock and AutoDock Vina are enrichment factor (EF), receiver operating characteristics, and area under the curve (AUC).Results: The dimensions of grid boxes were 30×30×30 (AutoDock) and 11.25×11.25×11.25 (AutoDock Vina). The EF 1% and AUC values obtained from the AutoDock are 7.74 and 0.73, respectively, and in the AutoDock Vina are 4.6 and 0.77, respectively. Based on the virtual screening results, the top six compounds obtained using AutoDock (binding energy ranging from −7.84 kcal/mol to −8.79 kcal/mol) include: Azadiradione, cylindrin, lanosterol, sapogenin, simiarenol, and taraxerol. The top seven compounds (binding energy ranging from −8.8 kcal/mol to −9.4 kcal/mol) obtained using AutoDeck Vina include: Bryophyllin A, diosgenin, azadiradione, sojagol, beta-amyrin, epifriedelinol, and jasmolactone C.Conclusions: Only azadiradione was obtained from the virtual screening conducted using both types of software; it interacts with the active region in BACE1 at residue Trp 76 (AutoDock result) and Thr 232 (AutoDock Vina result).  

scholarly journals Synthesis and ADMET Study of Some 1, 8-Naphthyidine and Quinoline 3-Carboxylic Acid Derivatives

2021 ◽  
Vol 9 (11) ◽  
pp. 1932-1938
Author(s):  
Vinod Kumar Gurjar
Keyword(s):  
Carboxylic Acid ◽  
Virtual Screening ◽  
Heterocyclic Compound ◽  
Mechanism Of Action ◽  
In Silico ◽  
Heterocyclic Compounds ◽  
Analytical Techniques ◽  
Drug Resistant ◽  
Alternate Mechanism ◽  
Selection Of

Abstract: The extremely drug resistant may be a worldwide public ill health in recent years. Molecules with newer targets and an alternate mechanism of action is an urgent requirement of improvement of latest drugs. The utilization of heterocyclic compounds has been increased dramatically over the last 70 years due to their wide selection of technical applications and their favorable environmental and toxicological properties The 1,8-naphthyridine and quinoline 3-carboxylic acid derivatives that we'll manufacture during this method will change the potency and specificity of fluoroquinolones. Taking under consideration the findings, the goal is to style and manufacture 1, 8-naphthyridine and quinoline 3-carboxylic acid derivatives. The synthesized compounds are going to be characterized using multiple analytical techniques, virtual screening, and in-silico ADME/T prediction. Keywords: 1, 8-Naphthyridine, Quinoline, ADMET, Heterocyclic Compound

Sign in / Sign up

Export Citation Format

Share Document