List of Articles Molecular docking

• Open Access Article
  • Abstract Page
  • Full-Text
  
  1 - In silico study to Identify New Inhibitors of Staphylococcus aureus (S. aureus) Sortase A
  hassan sahebjamee Mehr Ali Mahmood Janlou
  Introduction: Inhibition of key enzymes in bacteria that exert low evolutionary pressure can be a drug development strategy for bacterial antibiotic resistance. Sortase A (Srt A) is a transpeptidase that is widely used in site-specific protein modification. This enzyme More

  Introduction: Inhibition of key enzymes in bacteria that exert low evolutionary pressure can be a drug development strategy for bacterial antibiotic resistance. Sortase A (Srt A) is a transpeptidase that is widely used in site-specific protein modification. This enzyme has a key function in the interactions between Staphylococcus aureus and the host and has been considered a promising target for the drug development of resistant bacteria. To date, some Srt A inhibitors have been discovered most of them are derived from flavonoid compounds, like myricetin. Aim: Since computational methods for monitoring the behavior of biomolecules at the microscopic level are more accurate and cost-effective, therefore, in this research, our goal is to use computational methods to find similar molecules but with higher binding and inhibitory effect than myricetin. Materials and Methods: In this study, we used computational methods such as structure-based virtual screening, molecular docking, MM-PBSA approach, and MD simulation. A molecular docking approach was used to understand protein-ligand interactions and inhibition constants in terms of affinity. MD simulation technique was used to monitor the conformational changes of Srt A enzyme. After the MD simulation studies, the MM-PBSA approach was used to interpret the binding free energy. Results: First, Chemspider's chemical library was screened by the "Similarity search" method, in which myricetin was placed as a reference molecule. The second stage of screening was done using PyRx software, so that the top 10 compounds were carefully selected based on their inhibitory potential from the set of ligands obtained from the previous stage. These compounds were subjected to Autodock4.2 for molecular docking. As a result, it was observed that compound-73945561 has a higher inhibitory effect than myrsteine. To investigate the stability and efficiency of ligand binding mode, free Srt A, its complexes with myrsteine and the best selected compound were subjected to 50s molecular dynamics simulation. MD simulation results showed that compound-73945561 had better binding profiles and interactions than myrsteine as a reference inhibitor, and steadily unstable behavior was observed in the docking complex. Conclusion: Overall, compound-73945561 may serve as a new inhibitor or provide a scaffold for further optimization toward the design of more potent SortA inhibitors. The development of such inhibitors would be an essential strategy against resistant bacteria. Manuscript profile
• Open Access Article
  • Abstract Page
  • Full-Text
  
  2 - Investigating the Interaction between SSRI Drugs and Human Serum Albumin: Unraveling the Key Players in Antidepressant Delivery
  Vajagathali  Mohammed Nikitha Shalom  Richard
  10.22034/JCHR.2024.1087639
  Antidepressant drugs are medications used to treat various types of depressive disorders. They work by altering the balance of chemicals in the brain called neurotransmitters, which are involved in regulating mood. Selective Serotonin Reuptake Inhibitor (SSRI) is a clas More

  Antidepressant drugs are medications used to treat various types of depressive disorders. They work by altering the balance of chemicals in the brain called neurotransmitters, which are involved in regulating mood. Selective Serotonin Reuptake Inhibitor (SSRI) is a class of antidepressant drugs that specifically target the neurotransmitter serotonin in the brain. They work by blocking the reuptake of serotonin, which increases the concentration of serotonin in the synaptic gap between neurons. HSA plays a crucial role as a transport protein, facilitating the delivery of hormones and various other ligands to their specific destinations within the body. The interaction of SSRI drugs with HSA and their binding mechanism in the HSA-SSRI system has not been extensively studied so far. The primary objective of this study is to investigate the binding affinity (BA) of SSRI drugs with HSA and identify the amino acids that bind to the antidepressant drug. The HSA protein structure (PDB ID: 1AO6) has been downloaded from the Protein Data Bank, and the SSRI antidepressant drugs structure were generated using ChemDraw. Our docking results showed that the SSRI drugs had a significant binding affinity (BA) (more negative than -5.0) with the HSA protein. Among them, the highest BA was found with vilazodone (-8.6), and the lowest BA was observed with escitalopram (-6.1). This suggests that SSRI drugs can bind to the HSA protein, potentially facilitating their transport through the bloodstream. HSA binding can also influence the drug's free concentration, which is the active form available for interaction with its target receptors in the brain. Manuscript profile
• Open Access Article
  • Abstract Page
  • Full-Text
  
  3 - Synthesis, Evaluation of New Imidazolidin-4-one and Thiazolidine -4- one compound on Insulin in the Serum of Type 1 Diabetes Albino Rats
  Laith G. Atiya Omar M. Yahya Salim J. Mohammed
  10.22034/JCHR.2024.1088052
  This paper includes the synthesis of new imidazolidine-4-one and thiazolidine-4-one derivatives derived from 4-(2,4-dichlorophenoxy) butyric acid (1) by multistep reaction, the first step synthesis ester (2) by the esterification reaction of 4-(2,4-dichlorophenoxy) buty More

  This paper includes the synthesis of new imidazolidine-4-one and thiazolidine-4-one derivatives derived from 4-(2,4-dichlorophenoxy) butyric acid (1) by multistep reaction, the first step synthesis ester (2) by the esterification reaction of 4-(2,4-dichlorophenoxy) butyric acid with ethanol in the presence of sulfuric acid. Ester namely ethyl 4-(2,4-dichlorophenoxy) butanoate (2) was converted to the corresponding 4-(2,4-dichloro phenoxy)butane hydrazide (3) by reaction with hydrazine hydrate after those hydrazones (4a-f) derivatives were obtained by the reaction of carboxylic acid hydrazide (3) with various substituted aromatic aldehydes, this hydrazone were used to synthesize some new heterocyclic compounds by the hydrazones (4a-f) with Phenyl Alanine and thioglycolic acid to prepare imidazolidine-4-one(5a-e) and thiazolidine-4-one (6a-d) compounds respectively. The molecular docking study was carried out with the essential enzyme Insulin (PDB 1i144) responsible for Diabetes, suggesting that (4a-e) are the most active derivatives of the series that is responsible for diabetes, for some of the compounds that were prepared in this study. It was found that compounds (4a-e) are the most active derivatives. All newly synthesized compounds in this study were confirmed by physical and spectral (FT-IR, 1H NMR, and 13C NMR) analysis. Manuscript profile