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Home > Identification of Potent Inhibitors Against Potential Drug Target for Schizophrenia Through Virtual Screening Approach

Identification of Potent Inhibitors Against Potential Drug Target for Schizophrenia Through Virtual Screening Approach

Thesis Info

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External Link

Author

Hifza Saleem

Institute

Virtual University of Pakistan

Institute Type

Public

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Software Engineering

Language

English

Link

http://vspace.vu.edu.pk/detail.aspx?id=239

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676721003878

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Schizophrenia is related with physiological condition. It effects brain sections including the prefrontal cortex, the basal ganglia as well as limbic system. There are certain neurotransmitters present in the brain such as dopamine. When level of dopamine is disturbed it causes schizophrenia. Environmental factors like stress, depression and anxiety also contribute to schizophrenia. Several drugs including first and second generation are available to provide treatment against schizophrenia. Second generation drugs have better results and less side effects than first generation. Clozapine is second generation drug which was recommended as best drug for schizophrenia. It rebalances dopamine and helps to treat the patients of schizophrenia as well as diminishing of suicidal thoughts. Therapies and counselling also help to overcome this disorder. Dopamine Beta Hydroxylase catalyzes the synthesis of norepinephrine. Dopamine beta hydroxylase activity was suggested as a biological marker for schizophrenia alongside other psychiatric disorders. Here our goal is to design best inhibitor against schizophrenia with low cost and less side effects because the recommended drugs for schizophrenia are expensive and have many side effects. For this study, different databases were used. Structure and potential lead molecules were identified by the help of structure as well as ligand based virtual screening. AutoDock is used for virtual screening based on target. For ligand based virtual screening ZINC 15 database was used. Compounds were selected and further screened by using PyRx software. The ligands with less binding affinity were selected for analysis. Structure and interactions are viewed in DS visualizer tool and protein ligand explorer. Virtual screening is used for computational screening of huge library of chemicals for the compounds which supplement targets of known structure by testing them experimentally. Ligands were screened by using PyRx server and ZINC 15 server. Auto dock is used to dock ligands against drugs and display results. On the bases of binding energy and affinities ligands were Chosen. Top 10 potent inhibitors displayed high docking scores as well binding affinity and energy. Drugs can be further analyzed by use of vitro and in vivo analysis
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سچائی دی برکت

سچائی دی برکت

پرانے وقتاں دی گل اے کہ اک وار حضرت شیخ عبدالقادر جیلانی بال پن وچ علم حاصل کرن لئی اک قافلے دے نال بغداد توں روانہ ہوئے۔ ٹرن ویلے آپ دی والدہ محترمہ نے چالی دینار آپ دی قمیض دے اندر سی دتے تے نصیحت کیتی کہ پتر ہمیشہ سچ بولنا ایں۔ بھانویں کنی وی مشکل کیوں نہ بن جاوے۔ اتفاق دی گل اے کہ رستے وچ اوس قافلے اتے ڈاکواں نے حملہ کر دتا تے سارے بندیاں دا مال کھو لیا۔ جدوں ڈاکو واری واری پر بندے دی تلاشی لے رہے سن تاں اک ڈاکو نے آپ کولوں پچھیا کہ تیرے کول کیہ اے؟ آپ نے جواب دتا میرے کول چالی دینار نیں۔ جو میری والدی نے سفر تے روانہ ہوون توں پہلاں میری قمیض وچ سی دتے سن۔ ڈاکو نے آپ دی ایس گل اتے اعتبار نہ کیتا۔ ہر جدوں ویکھیا تاں واقعی قمیض اندر دینار سن۔ ڈاکو بہت حیران ہویا تے آپ نوں پھڑ کے اپنے سردار کول لے گیا۔ تے ساری گل سردار نوں دسی۔ سردار نے آکھیا۔ توں سچ بول کے اپنی رقم کیوں گوائی۔ جے توں جھوٹ بول دیندا تاں تیرے اُتے کسے نوں شک وی نئیں سی ہونا کہ تیرے کول اینی وڈی رقم اے۔ آپ نے فرمایا کہ میری والدہ نے سفرو شروع کرن ویلے ایہہ نصیحت کیتی سی کہ جھوٹ نئیں بولنا۔ ہمیشہ سچ بولنا ایں۔ میں جھوٹ بول کے اپنے والدہ دے حکم دی خلاف ورزی نئیں کر سکدا۔ ایس جواب نے سردار نوں بہت متاثر کیتا۔ اوس دے دل وچ خیال آیا کہ ایہہ منڈا اپنی ماں دے حکم دی خلاف ورزی نئیں کرسکدا۔ میں اپنے ربّ دا ایناں نافرمان آں کہ اوس دی کوئی وی گل نئیں مندا۔ سردار نے اوسے ویلے سچے دل توں توبہ کیتی تے لٹیا...

تعلیل احادیث صحیحین: امام ابو حاتم وأبو زرعہ كی آراء كا تنقیدی جائزہ

It is unique and high distinction of the Muslim Ummah that they have saved the teachings of Prophet Muhammad (PBUH). There have been high profile scholars who had dedicated their lives for the investigation of veracity and authenticity of Ḥadīths. They have been sifting the narrators of Ḥadīths through the myriad of resources to endorse or reject the authenticity of Ḥadīths. Amongst these eminent scholars, Imām Abū Ḥātim and Imām Abū Zur'ah, who made great contribution in the field of Elal Ḥadīth. Both criticized Aḥādīth some of which are quoted in Sahih Imām Bukhārī and Sahih Imām Muslim. Both books have always been taken as an authentic source for the veracity of Aḥādīth. However, they have pointed out a few such aspects which are vital for keeping the veracity and authenticity of Aḥādīth. This article is an attempt to study those Aḥādīth as quoted in the two above mentioned books and were criticized by Imām Abū Ḥātim and Abū Zur’ah in their book Elal Ḥadīths, by comprising with sayings of the concerned scholars. The most accurate aspect has been elaborated.

Influence of Zinc on Maize and Wheat in Combination With Organic Amendments under Calcareous Soil

Organic amendment due to their variable mineralization, immobilization and adsorption capabilities need different management strategies and integration with chemical fertilizers for maximum benefits. in this regard a series of laboratory and field experiments were conducted to evaluate the role of Farmyard manure (FYM), poultry manure (PM) and biochar (BC) in Zn availability under diverse calcareous soils of Peshawar (16.6 % CaCO3) and Charsadda (6.5 % CaCO3). These studies included Zn adsorption as influenced by these amendments in Peshawar soil [Piedmont alluvium, silty clay loam, Ustochrept] followed by incubation experiment for evaluating their role in improving soil [Zn]. Finally, the effect of amendments and applied Zn was studied in field conditions in both soils for two seasons. The first season crop was maize to which these amendments and Zn levels were applied whereas the wheat was used for their residual effect. The adsorption of Zn was assumed to be the difference between initially applied Zn (IZnA) and equilibrium Zn concentration (EZnC) in soil solution after 20 h continuous shaking. The soils amended with FYM, PM or BC each at 10 g kg-1 exhibited higher Zn adsorption (x/m) at higher IAZn (40 mg to 360 mg Zn L-1) but at lower IZnA < 20 mg Zn L-1 the reverse was observed. The data in non-treated soils were fit to both Langmuir and Freundlich models but in treated soils these models were fit only when the data for initial IAZn were disregarded. The higher maximum adsorption potential b (in case of Langmuir) and K (in case of Freundlich) values as well as maximum buffering capacity (MBC) in amended soil reveals the role of organic amendments in maintaining Zn in soil solution and availability to plants. The adsorption maximum as indicating by b and K was higher for BC followed by FYM but MCB and 1/n values that reflect the buffering capacity were higher for FYM than BC or PM. The lower adsorption at IZnA < 20 mg Zn L-1 but higher at > 20 mg Zn L-1 for amended soil suggests its contrasting effect at different IZnA levels. This reveals that organic amendments will increase the Zn nutrition in low concentrated Zn soils but on the other side can help in reducing its availability in highly contaminated soils. The incubation study was conducted to evaluate the comparative role of FYM, PM and BC in maintaining soil Zn of high limed, Peshawar and low limed, Charsadda soils during 84 days of incubation. The soils were first amended with the given organic xvi amendments at 10 g kg-1 and then supplied with Zn levels at 0, 1.5 and 3.0 mg kg-1 soil. The treatments were arranged in completely randomized design with 4 (amendments type) x 3 (Zn levels) x 2 (soil types) factorial arrangements replicated three times. Significantly higher AB-DPA extractable [Zn] levels were observed by PM followed by FYM in the initial intervals but by BC after 56 d of incubation suggesting its increasing role in soil fertility in long run. The combine application of amendments with Zn levels, further improved the recovered AB-DTPA extractable Zn at given incubation advocating the potential advantage of integrated use of organic and inorganic amendments in the given soils. Among amendments, the PM+Zn exhibited higher [Zn] in both soils followed by FYM+Zn. However, the effect of BC+Zn which remained lower to FYM+Zn in both soils at earlier incubation intervals superseded it at later stage affirming the potential role of BC in the long run. This incubation study corroborates the field trials where the BC+Zn was better in wheat whereas the FYM+Zn in maize. In the field experiments, Zn at 0, 3 and 6 kg ha-1 were applied alone or in combination with FYM, PM or BC each at 20 t ha-1 in both sites. After maize, the same plots were sown with wheat crop for residual effect. Growth and yields of first season maize and succeeding wheat crop increased with increase in Zn levels and amendment application but the response was comparatively higher in high limed Peshawar than Charsadda soil that may be attributed to its initially lower fertility and poor soil conditions. Among amendment, PM showed better performance in increasing crop growth and yields in both locations and crops followed by FYM in maize but in succeeding wheat the biochar became more effective withstanding statistically at par to both PM and FYM. This increasing promising effect of BC with time reveals its lower but long lasting effects in crop production. The application of Zn with amendments also significantly increased the grain Zn and postharvest soil [Zn] in both locations and crops. PM was more effective but with either 3.0 or 6.0 kg Zn ha-1 it induced similar increases over control in contrast to FYM and BC where grain Zn increased with increase in applied Zn levels. This could be attributed to high Zn contents in PM that need less applied Zn. Results concluded that application of PM with 3.0 kg Zn kg-1 and FYM and BC with 6.0 kg Zn ha-1 would be the optimum levels for first season crops but in the succeeding crops as residual effects higher Zn application would be required irrespective of amendment type in the given soil and climatic conditions. Furthermore, the application of BC is recommended for long lasting results but its initial higher cost may hinder its application at larger scale Key words: Organic amendments, zinc, plant growth, Zn adsorption, biochar, isotherm model, , calcareous soil