Purification and Characterization of a Novel Broad-spectrum Bacteriocin from Bacillus licheniformis MKU3

Nagarajan Kayalvizhi,Paramasamy Gunasekaran 한국생물공학회 2010 Biotechnology and Bioprocess Engineering Vol.15 No.2

A bacterial strain Bacillus licheniformis MKU3,isolated from slaughterhouse sediments showed a strong antimicrobial activity. The antimicrobial substance produced by this strain was found to be a protein that inhibited a broad range of bacterial strains, such as Bacillus sp.,Staphylococcus sp., Streptococcus sp., and Listeria monocytogenes. The antimicrobial peptide was purified to homogeneity by cut off membrane filtration followed by gel filtration chromatography. The purified protein with low molecular mass (< 8 kDa) was resolved as single band on Tricine SDS-PAGE. This protein was stable at 100oC for 10 min, but lost its activity at 121oC in 15 min. It was resistant to the proteolytic action of trypsin, proteinase K,and pronase E and stable within a wide range of pH (3.0~11.0). This protein exhibited lytic activity on selected indicator strain Kurthia gibsonii GCS6.

3D-QSAR Studies on 2-(indol-5-yl)thiazole Derivatives as Xanthine Oxidase (XO) Inhibitors

Nagarajan, Santhosh Kumar,Madhavan, Thirumurthy The Basic Science Institute Chosun University 2015 조선자연과학논문집 Vol.8 No.4

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMFA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMFA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMFA models were generated using different alignments and the best model yielded a cross-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMFA models was found to be $r^2_{pred}$0.653. The CoMFA study revealed that the $R_3$ position of the structure is important in influencing the biological activity of the inhibitors. Electro positive groups and bulkier substituents in this position enhance the biological activity.

3D-QSAR Studies of 8-Substituted-2-aryl-5-alkylaminoquinolines as Corticotropin-releasing Factor-1 Receptor Antagonists

Nagarajan, Santhosh Kumar,Madhavan, Thirumurthy The Basic Science Institute Chosun University 2015 조선자연과학논문집 Vol.8 No.3

Corticotropin-releasing actor receptors (CRFRs) activates the hypothalamic pituitary adrenal axis, one of the 2 parts of the fight or flight response to stress. Increased CRH production has is associated with Alzheimer's disease and major depression and hypoglycemia. In this study, we report the important structural and chemical parameters for CRFR inhibitors using the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolines. A 3D QSAR study, Comparative molecular field analysis (CoMFA) was performed. The best predictions were obtained for the best CoMFA model with a $q^2$ of 0.607 with 6 components and $r^2$ of 0.991. The statistical parameters from the generated CoMFA models indicated that the data are well fitted and have high predictive ability. The contour map resulted from the CoMFA models might be helpful in the future designing of novel and more potent CRFR derivatives.

3D Structure Prediction of Thromboxane A2 Receptor by Homology Modeling

Nagarajan, Santhosh Kumar,Madhavan, Thirumurthy The Basic Science Institute Chosun University 2015 조선자연과학논문집 Vol.8 No.1

Thromboxane A2 receptors (TXA2-R) are the G protein coupled receptors localized on cell membranes and intracellular structures and play pathophysiological role in various thrombosis/hemostasis, modulation of the immune response, acute myocardial infarction, inflammatory lung disease, hypertension and nephrotic disease. TXA2 receptor antagonists have been evaluated as potential therapeutic agents for asthma, thrombosis and hypertension. The role of TXA2 in wide spectrum of diseases makes this as an important drug target. Hence in the present study, homology modeling of TXA2 receptor was performed using the crystal structure of squid rhodopsin and night blindness causing G90D rhodopsin. 20 models were generated using single and multiple templates based approaches and the best model was selected based on the validation result. We found that multiple template based approach have given better accuracy. The generated structures can be used in future for further binding site and docking analysis.

Theoretical Structure Prediction of Bradykinin Receptor B2 Using Comparative Modeling

Nagarajan, Santhosh Kumar,Madhavan, Thirumurthy The Basic Science Institute Chosun University 2016 조선자연과학논문집 Vol.9 No.4

Bradykinin receptor B2, a GPCR protein, binds with the inflammatory mediator hormone bradkynin. It plays an important role in cross-talk between the renin-angiotensin system (RAS) and the kinin-kallikrein system (KKS). Also, it is involved in many processes including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Hence, studuying the structural features of the receptor becomes important. But the unavailability of the three dimensional structure of the protein makes the analysis difficult. Hence we have performed the homology modelling of Bradykinin receptor B2 with 5 different templates. 25 different homology models were constructed. Two best models were selected based on the model validation. The developed models could be helpful in analysing the structural features of Bradykinin receptor B2 and in pathophysiology of various disorders related to them.

Comparative Molecular Similarity Indices Analysis (CoMSIA) of 8-substituted-2-aryl-5-alkylaminoquinolines as Corticotropin-releasing factor-1 Receptor Antagonists

Nagarajan, Santhosh Kumar,Madhavan, Thirumurthy The Basic Science Institute Chosun University 2016 조선자연과학논문집 Vol.9 No.4

Corticotropin-releasing factor receptors (CRFRs) activate the hypothalamic-pituitary-adrenal axis, which is an integral part of the fight or flight response to stress. Increase in CRH level is observed in Alzheimer's disease and major depression and hypoglycemia. Here, we report on the relevant physicochemical parameters required for the CRFR inhibitors. Comparative molecular similarity indices analysis (CoMSIA) was performed with the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolinesas CRFR inhibitors. The best predictions were obtained for the best CoMSIA model with a $q^2$ of 0.576 with 6 components and $r^2$ of 0.977. The statistical parameters from the generated CoMSIA models indicated that the data are well fitted and have high predictive ability. CoMSIA contour maps could be useful in the designing of more potent and novel CRFR derivatives.

3D QSAR Study of 2-Methoxyphenylpiperazinylakanamides as 5-Hydroxytryptamine (Serotonin) Receptor 7 Antagonists

Nagarajan, Santhosh Kumar,Madhavan, Thirumurthy The Basic Science Institute Chosun University 2016 조선자연과학논문집 Vol.9 No.2

5-hydroxytryptamine (serotonin) receptor ($5-HT_7R$) 7 is one of G-Protein coupled receptors, which is activated by the neurotransmitter Serotonin. After activation by serotonin, $5-HT_7$ activates the production of the intracellular signaling molecule cyclic AMP. $5-HT_7$ receptor has been found to be involved in the pathophysiology of various disorders. It is reported that $5-HT_7$ receptor antagonists can be used as antidepressant agents. In this study, we report the important structural and chemical parameters for 2-methoxyphenylpiperazinylakanamides as $5-HT_7R$ inhibitors. A 3D QSAR study based on comparative molecular field analysis (CoMFA) was performed. The best predictions were obtained for the best CoMFA model with $q^2$ of 0.594 with 6 components, $r^2$ of 0.986, Fisher value as 60.607, and an estimated standard error of 0.043. The predictive ability of the test set was 0.602. Results obtained the CoMFA models suggest that the data are well fitted and have high predictive ability. The contour maps are generated and studied. The contour analyses may serve as tool in the future for designing of novel and more potent $5-HT_7R$ derivatives.

Structure Prediction of KiSS1-derived Peptide Receptor Using Comparative Modelling

Nagarajan, Santhosh Kumar,Madhavan, Thirumurthy The Basic Science Institute Chosun University 2016 조선자연과학논문집 Vol.9 No.2

KiSS1-derived peptide receptor, a GPCR protein, binds with the hormone kiss peptin. They are important in the neuroendocrine regulation of reproduction and in the secretion of gonadotrophin-releasing hormone. Thus, analysing the structural features of the receptor becomes important. However, the three dimensional structure of the protein is unavailable. Hence in this study, we have performed the homology modelling of KiSS1-derived peptide receptor with 5 different templates. 30 models were constructed using two platforms - Easymodeller and ITasser. The optimal models were chosen based on the model validation. Two models were selected after validation. The developed models could provide useful for analysing the structural features of KiSS1-derived peptide receptor and their pathophysiological role in various disorders related to them.

Mesoscopic numerical analysis of reinforced concrete beams using a modified micro truss model

Nagarajan, Praveen,Jayadeep, U.B.,Madhavan Pillai, T.M. Techno-Press 2010 Interaction and multiscale mechanics Vol.3 No.1

Concrete is a heterogeneous material consisting of coarse aggregate, mortar matrix and interfacial zones at the meso level. Though studies have been done to interpret the fracture process in concrete using meso level models, not much work has been done for simulating the macroscopic behaviour of reinforced concrete structures using the meso level models. This paper presents a procedure for the mesoscopic analysis of reinforced concrete beams using a modified micro truss model. The micro truss model is derived based on the framework method and uses the lattice meshes for representing the coarse aggregate (CA), mortar matrix, interfacial zones and reinforcement bars. A simple procedure for generating a random aggregate structure is developed using the constitutive model at meso level. The study reveals the potential of the mesoscopic numerical simulation using a modified micro truss model to predict the nonlinear response of reinforced concrete structures. The modified micro truss model correctly predicts the load-deflection behaviour, crack pattern and ultimate load of reinforced concrete beams failing under different failure modes.

NATURAL CONVECTION AROUND A HEAT CONDUCTING AND GENERATING SOLID BODY INSIDE A SQUARE ENCLOSURE WITH DIFFERENT THERMAL BOUNDARIES

NAGARAJAN NITHYADEVI,PERIYASAMY UMADEVI 한국산업응용수학회 2015 Journal of the Korean Society for Industrial and A Vol.19 No.4

Two-dimensional steady laminar natural convection around a heat conducting and generating solid body inside a square enclosure with different thermal boundaries is performed. The mathematical model is governed by the coupled equation of mass, momentum and energy. These equations are discretized by finite volume method with power-law scheme and solved numerically by SIMPLE algorithm with under-relaxation technique. Effect of Rayleigh number, temperature difference ratio of solid-fluid, aspect ratio of solid-enclosure and the thermal conductivity ratio of solid-fluid are investigated numerically for Pr = 0:7. The flow and heat transfer aspects are demonstrated in the form of streamlines and isotherms respectively.