A new approach in protein folding studies revealed the potential site for nucleation center

A new approach to predict the 3D structures of proteins by combining the knowledge-based method and Molecular Dynamics Simulation is presented on the chicken villin headpiece subdomain (HP-36). Comparative modeling is employed as the knowledge-based method to predict the core region (Ala9-Asn28) of the protein while the remaining residues are built as extended regions (Met1-Lys8; Leu29-Phe36) which then further refined using Molecular Dynamics Simulation for 120 ns. Since the core region is built based on a high sequence identity to the template (65%) resulting in RMSD of 1.39 Å from the native, it is believed that this well-developed core region can act as a 'nucleation center' for subsequent rapid downhill folding. Results also demonstrate that the formation of the non-native contact which tends to hamper folding rate can be avoided. The best 3D model that exhibits most of the native characteristics is identified using clustering method which then further ranked based on the conformational free energies. It is found that the backbone RMSD of the best model compared to the NMR-MDavg is 1.01 Å and 3.53 Å, for the core region and the complete protein, respectively. In addition to this, the conformational free energy of the best model is lower by 5.85 kcal/mol as compared to the NMR-MDavg. This structure prediction protocol is shown to be effective in predicting the 3D structure of small globular protein with a considerable accuracy in much shorter time compared to the conventional Molecular Dynamics simulation alone

IN SITU OPTHALMIC GEL WITH ION ACTIVATED SYSTEM

In situ gel with ion activated system which occurs as triggered by a change in the ionic strength. Osmotic gradient is a factor that determines the rate of gelation on the surface of the gel. Polymers play an important role in drug delivery from their dosage forms. Polymeric in gelling systems provides longer drug release compared to conventional delivery systems. The use of biodegradable and biocompatible polymers for in situ gel formulation makes the drug delivery system acceptable and controlled. Thus the continuous and prolonged release of the drug, biocompatibility characteristics makes the dose gel form in situ reliable. Polymers that are used in ion activated in situ gelation can be various, such as gelrite gellan gum, alginates, deacetylated gellan gum, anionic polymers (carbopol), cationic polymer (chitosan), non-ionic polymers (HPMC, Methylcellulose), thiolated polymer (thiomers), carbomer (polymer used in ophthalmic), polycarbophil (polymer used in ophthalmic). This review is written based on the data or information obtained by using several search engines and several scientific journals, using the keywords in situ gel with polymers, ion activated the system, and limited search years in 2010 and above

The Influence of Sequence Alignment Length of template on the Accuracy and Quality of Homology modelling: Human Cytochrome P450 2D6 (CYP2D6) case study

Homology modelling is one of the important alternative techniques to X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy in structural determination of protein. CYP2D6 drug metabolizing enzymes have extensively studied prior to the successful determination of its 3D structure using X-ray crystallography. This study is one of the earlier works being carried out before the crystal structure was solved. The enzyme is polymorphic and more than 80 different alleles have been identified. The aim of this study is to identify possible criteria to improve the quality of 2D6 model. Four mammalian crystal structures CYP2C8, CYP2B4, CYP2C9 and CYP2C5 were selected from protein databank as template for CYP2D6 model. Multiple sequence alignment between the selected target and template was performed. Secondary structure prediction was generated using CYP2D6 sequence and the 3D models built based on each template. The quality of the models was evaluated using Ramachandran’s plot. The final models were superimposed with CYP2D6 crystal structure. The result shows that not only the sequence identity is important for the template selection but also the alignment length of sequence. The secondary structure prediction of CYP2D6 sequence was found significantly matched the secondary structure prediction of the 3D structures of CYP2D6 models. The stereochemical quality of CYP2D6 models were found adequately satisfied the Ramachandran.plot requirements and comparable to the stereochemical quality crystal structure proteins used as templates and CYP2D6 crystal structure. The criteria set shows that CYP2C8 is the better template for homology modelling of CYP2D6 since it has scored lower E-value and longer alignment length, high sequence identity provided by ClustalW . In addition the secondary structure prediction of the model better matched the consensus and satisfy the criteria of Ramachandran’s plot as well it retained lowest RMSD value from the crystal structure. The study concludes to that the length of the sequence alignment is a critical factor in template selection it is also shows the important primary and secondary structure prediction.Keywords: Homology modelling, CYP2D6, CYP2C8, CYP2C9, CYP2B4, CYP2C5

4-Methyl-2-oxo-2H-chromen-7-yl 4-fluoro­benzene­sulfonate

In the asymmetric unit of the title compound, C16H11FO5S, the 2H-chromene ring is essentially planar, with a maximum deviation of 0.040 (2) Å. The dihedral angle between the 2H-chromene ring and the 4-fluoro­phenyl ring is 2.17 (8)°. One of the sulfonamide O atoms is approximately coplanar with the benzene ring [C—C—S—O torsion angle = 166.00 (14)°], whereas the other O atom lies well below the plane [C—C—S—O = −61.35 (17)°]. In the crystal, mol­ecules are connected by weak C—H⋯O hydrogen bonds, forming two-dimensional networks parallel to the ac plane

Exploring the molecular interactions between neoculin and the human sweet taste receptors through computational approaches

Neoculin is a sweet taste protein capable of modifying sour taste into sweet taste. Neoculin, along with other sweeteners, are received by the human sweet taste receptors T1R2 and T1R3. To date, there has been few studies regarding how neoculin interacts with the human sweet taste receptors in molecular level. In this study, computational approaches were applied to elucidate how neoculin interact with T1R2 and T1R3 at molecular level. In order to achieve this research, homology modeling for T1R2 and T1R3 was performed to predict their structure. A protein-protein docking study was conducted between neoculin and T1R2 and T1R3, which displayed a strong relationship with the previous experimental findings regarding the important residues of neoculin, and how they interact with the ATD domain of T1R3. These residues are His11, Asp91, Tyr21, Asn44, Arg48, Tyr 65, Val72, and Phe94. The best docked complexes were then subjected to molecular dynamics simulation for further analysis. The molecular dynamics simulation results showed the contributions of the important residues of neoculin in forming hydrogen bonds with the residues of the receptors. The binding energy between neoculin and each of T1R2 and T1R3 were also calculated. These results concluded that neoculin sweet taste and taste modifying abilities are only active when it binds to the amino terminal domain of T1R3

Molecular Docking Of Andrographolide To Rennin, HIV-Protease And Tyrosine Enzymes.

AutoDock 3.0 was used to dock andrographolide,a diterpenoid from the herb Andrographis Paniculata Nees, to the active site of Renin, HIV -1 Protease, and Tyrosine kinase enzymes. The andrographotide structure was prepared using Insight's ll Bui[der module

IN VITRO DRUG RELEASE STUDY OF CHLORAMPHENICOL IN SITU GEL WITH BASES MIXTURE OF POLOXAMER 407 AND HPMC BY OPTIMIZATION WITH FACTORIAL DESIGN

Objective: The objective of this study was to find the best base mixture composition (poloxamer 407 and HPMC) of chloramphenicol in situ gel formula based on in vitro property (Cumulative amount of drug release). Methods: The in vitro diffusion of chloramphenicol in situ gel study was carried out using franz diffusion cells to know the effect of the Critical Process Parameters (CPPs) as independent variables (poloxamer 407 and hydroxypropyl methylcellulose (HPMC)) on the Critical Quality Attribute (CQA) as dependent variable (cumulative amount of drug release) with 22 factorial design. Results: 22 factorial design of chloramphenicol in situ gel yielded 4 variations of poloxamer 407 and HPMC bases component in %w/v as follows, F1 (5:0.45), F2 (10:0.45) F3 (5:1) and F4 (10:1). The amount of drug release results from in vitro dissolution assay were 30.60% (F1), 45.64% (F2), 58.30% (F3), and 22.50%) (F4). Conclusion: Formula 3 (F3) was considered as the best formula component in terms of in vitro assay of chloramphenicol in situ gel with a desirability value of 0.58

Docking Of Different Enzymes With Quercetin

Flavonoids are a group of polyphenols that widely exists as colourful pigment for fruits,vegetables and herbs. Quercetin is one of the major components of flavonoids