Optimal Binding Features Research Articles

Protein targets in the red complex organisms binding with an herbal compound silymarin.

Periodontitis is attributed to the dental biofilm formation caused by various microbial changes that occurs in the biofilm. Red complex organisms are a group of organisms linked with periodontal diseases. Therefore, it is of interest to identify potential targets from the red complex organisms to bind with the herbal compound silymarin. We report a list of potential proteins having optimal drug like binding features with the herbal agent silymarin for further consideration. We used the STITCH v.5 pipeline using VICMPred and VirulentPred tools to identify such targets as potential virulent factors in the red complex organisms. We considered the strains of Porphyromonas gingivalis ATCC 33277, Treponema denticola ATCC 35405 and Tannerella forsythia ATCC 43037 in the red complex pathogens for this analysis. Protein targets in the red complex organisms with optimal binding features with the herbal compound silymarin were thus identified and reported for further consideration.

Molecular docking analysis of COX-2 for potential inhibitors.

Cyclooxygenase-2 (COX-2) is liked with breast cancer. Therefore, it is of interest to design and develop new yet effective compounds against COX-2 from medicinal plants such as the natural alkaloid compounds. We document the optimal binding features of aristolochicacid with COX-2 protein for further consideration.

Molecular docking analysis of α2-containing GABAA receptors with benzimidazoles derivatives.

It is of interest to study the binding capacity of "3-[2-(2-Amino-1H-benzo[d]imidazol-1-yl)ethyl]-1,3-oxazolidin-2-one" (OXB2) with the active site of gamma-aminobutyric acid (GABA) located in the GABA type A receptor (GABAAR) in comparison with different GABAA subtypes. Optimal binding features were observed with the α2β2γ2 isoform (-8 kcal/mol). This is similar (-7.3 and -7.2 kcal/mol, respectively) for subtypes (α3β2γ2 and α1β2γ2). This implies that OXB2 binds preferentially to subtypes associated with anxiety (α2- and/or α3-containing receptors) linked molecules than with the subtype associated with sedation (α1-containing receptors). It is further noted that molecular dynamics simulation data of the complex (OXB2-GABAAR) shows adequate structural stability in aqueous environment. Moreover, relevant ADMET data is found adequate for further consideration.

Molecular docking analysis of amyloid precursor protein with compounds from the Australian cowplant.

Amyloid precursor protein is linked with Alzheimer's disease (AD). The Australian cowplant Gymnema sylvestre is known in Indian and Chinese medicine. Therefore, it is of interest to screen the Amyloid precursor protein with compounds from the Australian cowplant. We report five compounds (Gymnemasaponin 5, Gymnemasin D, Gymnemoside A, Gymnemoside E, Gymnemoside F) derived from the Australian cowplant as the poteinal inhibitors of Amyloid precursor protein with optimal binding features for further consideration.

From sequence analysis of DPP-4 to molecular docking based searching of its inhibitors.

Literature data suggests that Dipeptidyl peptidase-4 (DPP-4) is a potential target for type 2 Diabetes Mellitus. Therefore, it is of interest to identify new DPP-4 inhibitors using molecular docking analysis. We document compounds such as STOCK1N-98884, STOCK1N-98881, and STOCK1N-98866 with optimal binding features with DPP-4 from the ligand database at https://www.ibscreen.com/ for further consideration.

Molecular docking analysis of Bcl-2 with phyto-compounds.

The Bcl-2 protein is liked in several cancers and drug resistance to therapy is also known in this context. There are many Bcl-2 inhibitors under clinical trials. It is of further interest to design new Bcl2 inhibitors from phyto compounds such as artesunate, bruceantin, maytansin, Salvicine, indicine N-oxide, kamebanin and oxyacanthine. We report the optimal binding features of these compounds with Bcl-2 for further consideration towards in vitro and in vivo validation.

Molecular docking of C-Jun-N-Terminal Kinase (Jnk) with amino-pyrimidine derivatives.

It is of interest to document the molecular docking of C-Jun-N-Terminal Kinase (Jnk) (known structure with PDB ID: 1PMN) with amino-pyrimidine derivatives in the context of Alzheimer's Disease (AD). We report the optimal binding features (binding energy, interacting residues, inter atomic hydrogen bonding patterns) of 11 amino-pyrimidine derivatives with Jnk for further consideration.

Identification of a novel dual-target scaffold for 3CLpro and RdRp proteins of SARS-CoV-2 using 3D-similarity search, molecular docking, molecular dynamics and ADMET evaluation

The new SARS-CoV-2 coronavirus is the causative agent of the COVID-19 pandemic outbreak that affected whole the world with more than 6 million confirmed cases and over 370,000 deaths. At present, there are no effective treatments or vaccine for this disease, which constitutes a serious global health crisis. As the pandemic still spreading around the globe, it is of interest to use computational methods to identify potential inhibitors for the virus. The crystallographic structures of 3CLpro (PDB: 6LU7) and RdRp (PDB 6ML7) were used in virtual screening of 50000 chemical compounds obtained from the CAS Antiviral COVID19 database using 3D-similarity search and standard molecular docking followed by ranking and selection of compounds based on their binding affinity, computational techniques for the sake of details on the binding interactions, absorption, distribution, metabolism, excretion, and toxicity prediction; we report three 4-(morpholin-4-yl)-1,3,5-triazin-2-amine derivatives; two compounds (2001083-68-5 and 2001083-69-6) with optimal binding features to the active site of the main protease and one compound (833463-19-7) with optimal binding features to the active site of the polymerase for further consideration to fight COVID-19. The structural stability and dynamics of lead compounds at the active site of 3CLpro and RdRp were examined using molecular dynamics (MD) simulation. Essential dynamics demonstrated that the three complexes remain stable during simulation of 20 ns, which may be suitable candidates for further experimental analysis. As the identified leads share the same scaffold, they may serve as promising leads in the development of dual 3CLpro and RdRp inhibitors against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

Molecular docking analysis of N-substituted oseltamivir derivatives with the SARS-Cov-2 main protease

The identification of chemotherapeutic drugs against Novel Coronavirus (2019-nCoV) is a significant requirement due to the rapid rise in deaths due to Corona Viral Infection all around the world. Therefore, it is of interest to document the molecular docking analysis data of 32 N-substituted Oseltamivir derivatives inhibitors of influenza virus H5N1 with the Novel Coronavirus main protease (2019-nCoV). We describe the optimal binding features of Oseltamivir derivatives with the SARS-Cov-2 main protease (Code PDB: 6LU7) for further consideration.

Modelling, docking and simulation analysis of Bisphenol A interaction with laccase from Trichoderma.

Fungal laccases are widely known for the degradation of recalcitrant xenobiotic compounds. Hence, it is of interest to study the interaction between laccase from Trichoderma laccase and Endocrine-Disrupting Chemical (EDC) named Bisphenol A. The molecular docking analysis of laccase from Trichoderma laccase with 23 xenobiotics and bisphenol A was completed. We show Bisphenol having optimal binding features (Glide score of -5.44 and the Glide energy -37.65 kcal/mol) with laccase from Trichoderma laccase.

Repurposing of known anti-virals as potential inhibitors for SARS-CoV-2 main protease using molecular docking analysis.

The new SARS-CoV-2 coronavirus is the causative agent of the COVID-19 pandemic outbreak that affected more than 190 countries worldwide with more than 292,000 confirmed cases and over 12,700 deaths. There is at the moment no vaccine or effective treatment for this disease which constitutes a serious global health problem. It is of interest to use a structure based virtual screening approach for the identification of potential inhibitors of the main protease of SARS-CoV-2 (Mpro) from antiviral drugs used to treat other viral disease such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. The crystallographic structure with PDB ID: 6LU7 of Mpro in complex with the inhibitor N3 was used as a model in the virtual screening of 33 protease inhibitors collected from the ChEMBL chemical database. Molecular docking analysis was performed using the standard AutoDock vina protocol followed by ranking and selection of compounds based on their binding affinity. We report 10 candidates with optimal binding features to the active site of the protease for further consideration as potential drugs to treat patients infected with the emerging COVID-19 disease.

Molecular modelling and docking analysis of pleurocidin (an antimicrobial peptide) like peptides with enterotoxin H from Klebsilla pneumonia.

Enterotoxin H is a key molecular target for replication and establishment of Klebsilla pneumonia in the host. Therefore, it is of interest to study the interaction of enterotoxin H with pleurocidin like peptides using molecular modelling (template PDB ID: 1YCE), Lig-Plot (ligand construction) and docking tools for therapeutic consideration. The hydrophobic pocket and the active site residues (Val 13, Met 16, Gly 25, Ala 25, and Ile 28) were identified using Cast P, Molegro and Sitehound tools. Docking results show that the pleurocidin like peptides interacts with the active sites of enterotoxin H with 300.96 docking score with optimal binding features.

Molecular docking based virtual screening of carbonic anhydrase IX with coumarin (a cinnamon compound) derived ligands.

It is of interest to design carbonic anhydrase IX (CAIX) inhibitors with improved features using molecular docking based virtual high through put screening of ligands. Coumarin (a cinnamon compound with pharmacological activity) is known as a potent phytal compound blocking tumor growth. Hence, a series of 17 coumarin derivatives were designed using the CHEMSKETCH software for docking analysis with CAIX. The catalytic site analysis of CAIX for binding with ligand molecules was completed using the SCHRODINGER package (2009). Thus, 17 ligands with optimal binding features with CAIX were selected following the calculation of ADME/T properties. We report ligands #41, #42, #19 and #15 showed good docking score, glide energy and hydrogen bond interactions without vdW clash. We further show that N-(3,4,5-trimethoxy-phenylcarbamoylmethyl) designated as compound #41 have the highest binding energy (-61.58) with optimal interactions with the catalytic residues (THR 199, PRO 201, HIS 119, HIS 94) of CAIX.

Combined e-pharmacophore based screening and docking of PI3 kinase with potential inhibitors from a database of natural compounds.

Phospho inositide 3-kinase (PI3 K) is a promising target for the design of anticancer drugs and is of significant concern in developing selective isoforms as inhibitors for cancer treatments. The results obtained from the computational analysis were selected based on Glide score and drug binding interaction features. Molecular docking studies and prime MM-GBSA energy calculations showed STOCK1N-77648 with optimal binding features for further consideration. The hydrogen bonding patterns between the top three molecules STOCK1N-91335, STOCK1N-70036 and STOCK1N-77648 and the target protein based on G-scores is reported. The STOCK1N-77648 ligand molecule has protein residue interactions similar to that of interactions with the known inhibitor copanlisib. These data illustrates selectivity of the small molecular PI3 K inhibitors through screening and molecular docking for further in vitro and in vivo consideration.

Molecular docking based design of Dengue NS5 methyltransferase inhibitors.

Dengue is a viral infection caused by RNA infection of the family Flaviviridae and spread by the Aedes mosquitoes. Dengue NS5 methyltransferase is a known drug target for the disease. Therefore, it is of interest to design potential inhibitors for the target using molecular docking analysis. Our analysis shows the binding of compounds STOCK1N-98943, STOCK1N-98872, STOCK1N-98956, STOCK1N-98865, and STOCK1N-98950 with the protein drug target with optimal binding features for further in vitro and in vivo evaluations.

Interaction of M(3+) Lanthanide Cations with Amide, Pyridine, and Phosphoryl O=PPh(3) Ligands: A Quantum Mechanics Study.

We report an ab initio quantum mechanical study on the interaction of M(n)()(+) cations (M(n)()(+) = La(3+), Eu(3+), Yb(3+), Sr(2+), and Na(+)) with model ligands L for lanthanide or actinide cations: several substituted amides, pyridines, and the phosphoryl-containing OPPh(3) ligand. The interaction energies DeltaE follow trends expected from the cation hardness and ligand basicity or softness in the amide series (primary < secondary-cis < secondary-trans < tertiary) as well as in the pyridine series (para-NO(2) < H < Me < NMe(2)). Among all ligands studied, OPPh(3) is clearly the best, while the (best) tertiary amide binds lanthanides slightly less than the (best) pyridine-NMe(2) ligand. In the lanthanide 1:1 complexes, the energy differences DeltaDeltaE as a function of M(3+) (about 40 kcal/mol for all ligands) are less than DeltaDeltaE in the pyridine series (up to about 90 kcal/mol) where marked polarization effects are found. The conclusions are validated by a number of methodological investigations. In addition to optimal binding features, we also investigate the directionality of ion coordination to the ligands and the effect of counterions and stoichiometry on the structural, electronic and energetic features of the complexes. The results are discussed in the context of modeling complexes of lanthanide and actinide cations and compared to those obtained with analogous Na(+) and Sr(2+) complexes.