scholarly journals NUMBER OF RUNS VARIATIONS ON AUTODOCK 4 DO NOT HAVE A SIGNIFICANT EFFECT ON RMSD FROM DOCKING RESULTS

2021 ◽  
Vol 8 (6) ◽  
pp. 476-480
Author(s):  
M.R.F. Pratama ◽  
S. Siswandono
Keyword(s):  
Free Energy ◽  
Estrogen Receptor ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Linear Equation ◽  
Significant Contribution ◽  
Amino Acid Residues ◽  
Maximum Difference ◽  
Binding Inhibition ◽  
Free Energy Of Binding

The aim. The number of runs in the docking process with AutoDock 4 is known to play an important role in the validity of the results obtained. The greater the number of runs it is often associated with the more valid docking results. However, it is not known exactly how the most ideal runs in the docking process with AutoDock 4. This study aims to determine the effect of the number of runs docking processes with AutoDock 4 on the validity of the docking results.Materials and methods. The method used is the redocking process with AutoDock 4.2.6. The receptor used is an estrogen receptor with ligand reference estradiol (PDB ID 1GWR). Variations were made on the number of runs from 10 to 100 in multiples of 10. The parameters observed were RMSD, free energy of binding, inhibition constants, amino acid residues, and the number of hydrogen bonds.Results. All experiments produce identical bond free energy, where the maximum difference in inhibition constant is only 0.06 nM. The lowest RMSD is indicated by the number of runs of 60, with a RMSD value of 0.942. There is no linear relationship between the number of runs and RMSD, with R in the linear equation of 0.4607.Conclusion. Overall, the number of runs does not show a significant contribution to the validity of the results of docking with AutoDock 4. However, these results have only been proven with the receptors used.

scholarly journals IN SILICO PREDICTION AND MOLECULAR DOCKING STUDIES OF BIOLOGICAL ACTIVITY OF HYDROACRIDINE (QUINOLINE) DERIVATIVES

2021 ◽  
Vol 87 (5) ◽  
pp. 38-52
Author(s):  
Nikolay Smetanin ◽  
Sofia Tokarieva ◽  
Svetlana Varenichenko ◽  
Oleg Farat ◽  
Victor Markov
Keyword(s):  
Free Energy ◽  
Biological Activity ◽  
Molecular Docking ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Binding Free Energy ◽  
Moderate Activity ◽  
Amino Acid Residues ◽  
Anticonvulsant Agents ◽  
Anti Inflammatory

To find biological activity among easily available 2-[(4S,4’S/4R,4’R)-2’,5’-dioxo-2,3,5,6,7,8-hexahydro-1H-spiro[acridine-4,3’-pyrrolidin]-4’-yl]-N-aryl-acetamide, (4S/4R)-4-[(3R/3S)-1-(2-aryl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile, (3S/4R)-3-[(3R/4S)-9-chloroacridine(quinoline)-4-yl]-1-N-aryl)pyrrolidine-2,5-diones. Methods: Organic synthesis, spectral methods, and molecular docking. We investigated by molecular docking the potential biological activity of previously synthesized compounds containing acridine and pyrrolidine-2,5-diones fragments in their structure, as well as synthesized in this work N’-hydroxy-1,2,3,4,5,6,7,8-octahydroacridine-4-carboximidamide. Based on the literature data, 3 directions of searching for the biological activity of the synthesized compounds have been chosen: cholinesterase inhibitors, anti-inflammatory, and anticonvulsant agents. As inhibitors of acetylcholinesterase and butylcholinesterase, substances with good binding free energy and hydrogen bonds with the desired amino acid residues of the Glu-His-Ser triad have been found among the tested compounds. The indicators of synthesized products have exceeded the literature data. The docking data for anti-inflammatory activity has revealed compounds with values above the docking data of the reference drugs - celecoxib and indomethacin. The compounds tested have shown moderate activity as anticonvulsant agents. 3-(7-bromo-9-chloro-1,2,3,4-tetrahydroacridin-4-yl)-1-(3-nitrophenyl)pyrrolidine-2,5-dione is potentially promising as an acetylcholinesterase inhibitor due to its high binding free energy (-13.7 kcal/mol) and hydrogen bonds with two amino acid residues Ser200, His440. Compound (4S/4R)-4-[(3R/3S)-1-(3-nitrophenyl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile has proved to be the best as an anti-inflammatory agent. The presence of a pyrrolidine-2,5-diones fragment increases the indicators of the biological activity of the synthesized compounds in comparison with just acridine derivatives.

scholarly journals The cyclol hypothesis and the “globular” proteins

1937 ◽  
Vol 161 (907) ◽  
pp. 505-524 ◽  
Keyword(s):  
Amino Acid ◽  
Hydrogen Bonds ◽  
Ad Hoc ◽  
Globular Proteins ◽  
The Body ◽  
Amino Acid Residues ◽  
Native Protein ◽  
Orderly Arrangement

A number of facts relating to proteins suggest that the polypeptides in native protein are in a folded state (Astbury 1933, 1934; Astbury and Street 1930, 1931; Pryde 1931; Wrinch 1936 a , b , c , 1937 a ; Langmuir, Schaefer and Wrinch 1937). The type of folding must be such as to imply the possibility of the regular and orderly arrangement of hundreds 01 amino-acid residues which to some extent at least is independent of the particular residues in question. We propose therefore to formulate all types of folding which are geometrically possible. Each hypothesis in turn can then be tested in two ways. We may consider its plausibility in itself: and having developed its implications to the farthest possible point, we may test it against known facts by ad hoc experiments. At present two types of folding have been suggested—by means of cyclol links (Wrinch 1936 a , b , c , 1937 a ; Langmuir, Schaefer and Wrinch 1937; Astbury 1936 a , b , c ; Frank, 1936) and by means of hydrogen bonds (Jordan Lloyd 1932; Jordan Lloyd and Marriott 1933; Mirsky and Pauling 1936; Wrinch and Jordan Lloyd 1936). The search for other types of folding is being continued. So far it has not proved possible to discard either theory on the grounds that the type of link postulated is out of the question. It is there­ fore very desirable to test these theories by means of their implications. Accordingly, on this occasion we consider (Wrinch 1937 b , c ) whether the cyclol theory can stand the test of the body of facts relating to the “globular” proteins, established by Svedberg and his collaborators (Svedberg and others 1929, 1930 a , b , 1934 a , b , 1935).

scholarly journals Analysis of molecular interactions of 8-gingerol compounds in Ginger (Zingiber officinale) as ACE Inhibitor

BIOEDUSCIENCE ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. 183-187
Author(s):  
Yohanes Bare ◽  
Mansur S ◽  
Aprianus Pani Pili ◽  
Maria Helvina
Keyword(s):  
Amino Acid ◽  
Hydrogen Bonds ◽  
Ace Inhibitor ◽  
Van Der Waals ◽  
Zingiber Officinale ◽  
Van Der Waals Forces ◽  
Amino Acid Residues ◽  
Protein Database ◽  
Discovery Studio ◽  
Software Analysis

Background: Hypertension is a disease with increasing characteristics of blood pressure. The ACE gene has a role in the conversion of ATI to ATII in hypertensive conditions. Healing is done by using the 8-gingerol content contained in ginger. The purpose of this study is to analyze the molecular interaction that occurs between 8-gingerol and ACE. Method: ACE model proteins (ID: 3bkk) were obtained from the Bank Data Protein database (PDB) through 8-gingerol ligands (CID: 168114) obtained from the PubChem database. ACE and 8-gingerol were docked by Discovery Study Client 4.1 software. Analysis of amino acid residues, binding energy, Van der Waals forces, and hydrogen bonds formed using Discovery Studio Client 4.1. Results: The interaction between 8-gingerol and ACE showed that there were seven amino acid residues that interacted with 8-gingerol, also found hydrogen bonds, hydrophobic and Van der Waals forces that strengthen and stabilize these bonds. Conclusion: the interaction of 8-ginger with the active side of ACE is determined as an ACE inhibitor, the inhibition is a significant effect on the obstruction of ACE conversion.

scholarly journals Identification of a putative anti-rheumatoid arthritis molecule by virtual screening

2020 ◽  
Vol 19 (6) ◽  
pp. 1255-1261
Author(s):  
Shazi Shakil ◽  
Adel M Abuzenadah ◽  
Suzan M. Attar ◽  
Omar Fathaldin ◽  
Rajaa Al-Raddadi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Free Energy ◽  
Virtual Screening ◽  
Thymidylate Synthase ◽  
Molecular Descriptors ◽  
Amino Acid Residues ◽  
Methotrexate Interaction ◽  
Inhibitor Design ◽  
Interaction Site ◽  
Free Energy Of Binding

Purpose: To propose an improved chemical skeleton whose scaffolds could be used for the design of future thymidylate synthase (TS)-inhibitors against rheumatoid arthritis. Methods: The drug discovery platform, ‘MCULE’, was employed for inhibitor-screening. The ‘methotrexate-interaction site’ in the crystal (PDB ID 5X66) was used as a target. One ‘RO5 violation’ was permitted. A maximum of ‘10 rotatable bonds’ and ‘100 diverse molecules’ were also allowed in the protocol. The ‘threshold similarity cut off’ was 0.7. The input values describing the remaining parameters were kept as ‘default’. The ‘Open Babel Linear Fingerprint’ was used for the analyses of molecular descriptors, followed by ADME-check. Results: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidine corresponding to the MCULE ID-7590816301-0-93 exhibited the overall best binding with TS. The free energy of binding was -8.6 kcal/mol. A total of 17 amino acid residues were significant for the binding interactions. Importantly, 9 residues were common to methotrexate binding. It satisfied pertinent ADME conditions. Conclusion: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidinemay emerge as a potent seed molecule for TS-inhibitor design in the context of rheumatoid arthritis. It has satisfied pertinent ADME features. However, there is need for further wet laboratory validation. Keywords: Anti-rheumatoid arthritis, Inhibitor design, Methotrexate, Seed molecule, Thymidylate synthase, Virtual screening

Conserved features of complexes of TATA-box binding proteins with DNA

2016 ◽  
Vol 14 (02) ◽  
pp. 1641007 ◽  
Author(s):  
Olga Zanegina ◽  
Evgeniy Aksianov ◽  
Andrei V. Alexeevski ◽  
Anna Karyagina ◽  
Sergei Spirin
Keyword(s):  
Comparative Analysis ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Protein Interaction ◽  
Binding Proteins ◽  
Tata Box ◽  
Amino Acid Residues ◽  
Protein Interface ◽  
Partial Symmetry ◽  
Dna Protein Interaction

A comparative analysis of all available structures of complexes of TATA-box binding proteins (TBPs) with DNA is performed. Conserved features of DNA–protein interaction are described, including nine amino acid residues that form conserved hydrogen bonds, 13 residues participating in formation of two conserved hydrophobic clusters at DNA–protein interface, and four conserved water-mediated contacts. Partial symmetry of conserved contacts reflects quasi-symmetry of TBP structure.

scholarly journals Crystal structure of Boc-(S)-ABOC-(S)-Ala-(S)-ABOC-(S)-Phe-OBn chloroform monosolvate

2015 ◽  
Vol 71 (10) ◽  
pp. 1193-1195
Author(s):  
Emmanuel Wenger ◽  
Laure Moulat ◽  
Baptiste Legrand ◽  
Muriel Amblard ◽  
Monique Calmès ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Carboxylic Acid ◽  
Hydrogen Bonds ◽  
Benzyl Ester ◽  
Protecting Groups ◽  
Amino Acid Residues ◽  
Hybrid Peptide ◽  
Proteinogenic Amino Acid ◽  
Solvent Molecules

In the title compound, phenyl (S)-2-[(S)-(1-{2-[(S)-(1-{[(tert-butoxy)carbonyl]amino}bicyclo[2.2.2]octan-2-yl)formamido]propanamido}bicyclo[2.2.2]octan-2-yl)formamido]-3-phenylpropanoate chloroform monosolvate, C42H56N4O7·CHCl3, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues of (S)-1-aminobicyclo[2.2.2]octane-2-carboxylic acid [(S)-ABOC], two amino acid residues of (S)-2-aminopropanoic acid [(S)-Ala] and (S)-2-amino-3-phenylpropanoic acid [(S)-Phe], and protecting groups oftert-butoxycarbonyl (Boc) and benzyl ester (OBn). The tetramer folds into a right-handed mixed 11/9 helix stabilized by intramoleculari,i + 3 andi,i − 1 C=O...H—N hydrogen bonds. In the crystal, the oligomers are linked by N—H...O=C hydrogen bonds into chains along thea-axis direction. The chloroform solvent molecules are intercalated between the folded chainsviaC—H...O=C interactions.

Functional Characterization of Chemosensory Protein AmalCSP5 From Apple Buprestid Beetle, Agrilus mali (Coleoptera: Buprestidae)

2020 ◽  
Author(s):  
Chunbo Li ◽  
Keke Sun ◽  
Dexian Li ◽  
Deguang Liu
Keyword(s):  
Amino Acid ◽  
Hydrogen Bonds ◽  
Binding Affinity ◽  
Functional Characterization ◽  
Management Strategies ◽  
Plant Secondary Metabolites ◽  
Invasive Pest ◽  
Chemical Information ◽  
Amino Acid Residues ◽  
Chemosensory Protein

Abstract In the sensitive and complex chemo-sensation system of insects, chemosensory proteins (CSPs) can facilitate the transfer of chemical information and play important roles for variable behaviors of insects. We cloned the chemosensory protein AmalCSP5 from antennae of the apple buprestid beetle (Agrilus mali Matsumura), a serious invasive pest of wild apple trees. Expression profiling showed that AmalCSP5 was expressed in various tissues, suggesting its significance in multiple physiological activities and behaviors of A. mali. AmalCSP5 was preferentially expressed in female antennae and male abdomens. AmalCSP5 was able to bind a variety of test volatiles, especially alcohols and esters. AmalCSP5 exhibited good binding affinity for all five test secondary compounds (i.e., procyanidin, phlorizin, kaemferol, chlorogenic acid, and rutin), suggesting its preferential binding abilities to nonvolatile host plant secondary metabolites and critical roles in gustatory perception of nonvolatiles. Tyr27 and Ser69 of AmalCSP5 could form hydrogen bonds with hexyl benzoate and hexyl hexanoate, respectively. Procyanidin, the best ligand among all test compounds, could form hydrogen bonds with three amino acid residues (i.e., Arg7, Leu8, and Lys41) of AmalCSP5. Thus, high ligand binding affinity for AmalCSP5 seemed to be dependent mainly on the formation of hydrogen bonds. The putative key amino acid residues of AmalCSP5 can be used as molecular targets for designing and screening new attractants and repellents for A. mali. Our results provide insights into binding interactions of AmalCSP5 with volatile and nonvolatile ligands, and a firm basis for developing eco-friendly management strategies of A. mali.

scholarly journals CHEMICAL STRUCTURE OPTIMIZATION OF LUPEOL AS ER-Α AND HER2 INHIBITOR

2018 ◽  
Vol 11 (6) ◽  
pp. 298 ◽  
Author(s):  
Mohammad Rizki Fadhil Pratama ◽  
Sutomo S
Keyword(s):  
Breast Cancer ◽  
Free Energy ◽  
Chemical Structure ◽  
Structure Optimization ◽  
Basis Set ◽  
Amino Acid Residues ◽  
Her2 Positive ◽  
Hartree Fock ◽  
Anticancer Properties ◽  
Free Energy Of Binding

Objectives: Lupeol, a triterpenoid isolated from Kasturi (Mangifera casturi) fruit has been known for having several pharmacological activities, including anticancer properties. Lupeol showed antiproliferative activity toward many cancer cells line including breast cancer. Lupeol showed promising potency as both ER-α and HER2 inhibitors, although still lower than known ER-α and HER2 Inhibitors. Chemical structure optimization of lupeol was predicted could increase the affinity of lupeol derivatives against ER-α and HER2. This study aims to determine lupeol derivative with the highest affinity against ER-α and HER2.Methods: All ligands were sketched and optimized using Gaussian 03W with Hartree–Fock method basis set 3-21G. Molecular docking was performed using Autodock 4.2.6 on several modified chemical structure of lupeol against active site of ER-α and HER2. The main parameter used was the free energy of binding and inhibition constants as affinity marker.Results: The docking results show that lupeol derivative with an amine group (Lupeol-2) and ethyl group (Lupeol-4) at position C3 provide the highest affinity with the free energy of binding and dissociation constant −12.24 kcal/mol and 1.07 nM for ER-α also −9.63 kcal/mol and 86.94 nM for HER2, respectively. Interestingly, although lupeol derivatives showed higher affinity toward ER-α, their amino acid residues were closer to the interaction on HER2.Conclusion: These results predict that lupeol have greater potential to be developed as a HER2 inhibitor. Further, derivate lupeol-4 should be potential to be developed as HER2-positive breast cancer therapy.

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