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Home > Computational Analysis of Metabolic Pathways and Protien-Protien Interactions Ppls of Clinically Significant Pathogens, and Identification of Inhibitors of Ppls

Computational Analysis of Metabolic Pathways and Protien-Protien Interactions Ppls of Clinically Significant Pathogens, and Identification of Inhibitors of Ppls

Thesis Info

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External Link

Author

Sufian, Muhammad

Program

PhD

Institute

University of Karachi

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Molecular Medicine

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12760/1/Thesis%20PhD%20Sufian.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725777076

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Salmonella enterica is a Gram-negative facultative anaerobic bacteria. It belongs to the family of Enterobacteriaceae. Infections caused by Salmonella species are major threat to the human and animal health. After 1-3 days of ingestion of contaminated food, the patient develops diarrhea, fever, vomiting, and abdominal cramps. The situation is exacerbated if not treated promptly. Whole genome sequencing projects of clinically significant serovars of S. enterica have opened new perspectives of medical research. Using the genomic data, novel approaches are being employed throughout the world to find new protein targets for drug designing and screening. Targeting the essential metabolic pathways of the bacteria is the approach which we have focused in our study. The protein sequence and metabolic pathway data of the core proteome of S. enterica was analyzed in comparison to that of Homo sapiens. Various computational tools (BLASTp, CD-HIT, and Shell scripting) and datasets (NCBI, DEG, and KEGG) were extensively utilized to find non-homologous and essential enzymes of the pathogen. We discovered 73 enzymes belonging to metabolic pathways found only in the bacteria but not in H. sapiens, and proposed them as potential drug targets. Later, we selected an essential outer membrane protein complex (LptD/E) of S. enterica involved in lipopolysaccharide assembly, as a target in search of an inhibitor of the PPI complex. Druggable sites at the interface of PPI were identified by PocketQuery followed by virtual screening of the ZINC database of commercially available compounds using the ZINCPharmer tool. Energy minimization and scoring of short-listed compounds was performed using SMINA. A rational screening of >10,000 compounds resulted in 3 compounds depicting favorable polar interactions and optimal conformation for binding with the LptD protein. We propose that this interaction may lead to block the LptD interaction with LptE and lipid molecules and in result may block the LPS assembly.
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قرآن مجید میں آیات ِاستفہام کی نوعیتیں

قرآن مجید میں آیات ِاستفہام کی نوعیتیں

 قرآن مجید کے مطالعہ سے واضح ہوتا ہے کہ اللہ تعالیٰ نے قرآن حمید میں متعدد مقامات پر انسانیت سے مختلف سوالات کیے ہیں جنہیں چار انواع میں تقسیم کیا گیا ہے،جن کی وضاحت کتبِ تفسیر کی روشنی میں اقوالِ سلف کے ساتھ ذکرکیا جاتا ہے:

فکر روایت اور تصوف: مغرب میں تصوف کے فروغ میں فکر روایت کا حصہ اور پاکستان کے اردو ادب پر اثرات

Islam and Mysticism or tasawuf have coexisted. Sufism has flourished in all Muslim dominated regions. Sufism is a mode of spirituality within Islam. Sufi schools teach three parts: Shariah, Tariqah and Haqiqh. In this article, traditional thoughts in Sufism and its impacts on the world especially in the region of Indo-Pak have been discussed. The shrines of Pakistani Sufis are the centers of inspiration for mysticism and spirituality that influence cultures and civilizations.

Analysis of Cognitive Demands of the Concepts Taught in General Science at 8Th Grade, Piagetian Developmental Levels of Students and Their Attitude Towards Learning of Science

The science textbook is one of the elements that can affect the quality of science education. The science textbook for any grade usually contains complicated and abstract concepts that students have to comprehend. It was evident from reported literature that these science concepts usually demand a higher level of reasoning ability from students while they have not yet attained that cognitive developmental level. One of the reasons is that Piaget‘s proposed age-stage model does not exist in its true sense and there is great variation in distribution of students at different Piagetian developmental levels (PDLs) throughout the world. This causes a mismatch between curricula demand and students‘ reasoning ability level. This mismatch is ultimately claimed to affect the students‘ attitude towards science learning. This study aimed to analyze the cognitive demand of the curricula of the 8th grade General Science textbook and patterns of Piagetian developmental levels and attitude towards science learning of students at 8th and 9th grades. Along with that, this study was also focused on exploring the effect of the mismatch between curricula demand and students‘ Piagetian developmental levels on students‘ attitude towards science learning. From 35 districts of Punjab province, three districts (Okara, Sargodha, & Rawalpindi) were conveniently selected for data collection. The data was collected from 1233 students of 8th and 9th grades of 37 government schools of these three districts. Curriculum Analysis Taxonomy (CAT) was applied to breakdown the 8th grade General Science textbook in terms of Piagetian developmental levels. Attitude of the students was measured by Attitude towards Science Learning scale (AtSL), a five point Likert scale, whereas the existing Piagetian developmental levels of the students were measured by administering of the Pendulum task (PRT III). Both research instruments were in Urdu (national language) and were personally administered by the researcher to ensure the reliability and a high rate of return of data. The mismatch between cognitive demands of the curricula of the 8th grade General Science textbook and existing Piagetian developmental levels of students of 8th grade was calculated. Later, the effect of this mismatch (between cognitive demands of the curricula of the 8th grade General Science textbook and existing Piagetian developmental levels of students at 8th grade) on attitude towards science learning was examined. It was found that respondents‘ parental profile regarding qualification and profession was very low. The contents of General science textbook of 8th grade were found to be distributed unevenly at different Piagetian developmental levels throughout textbook. Most of the respondents were at different sub-stages of the Concrete Operational level and a few were at Early Formal Operational level. It was further found that female students scored higher on the Pendulum task and also have better attitude towards science learning than male students. Similarly 9th grade students performed better on the Pendulum task and have more positive attitude towards science learning than 8th grade students. Rural and urban students were not significantly different in their attitude, whereas urban students performed significantly better on the Pendulum task. Students at different Piagetian developmental levels significantly differ in their attitude towards science learning. It was concluded that the respondents were from the lower socio-economic sector of society. Female students were more clustered at higher levels of cognitive development than male students, and female students have better attitude towards science learning. The attitude of the students increases with the increase in their reasoning ability. It was concluded that there exists a mismatch between students‘ reasoning ability and curricula demand and, with the increase in quantity of the mismatch, a decrease in attitude towards science learning occurs. It was recommended that the curriculum development experts need to develop a model in terms of Piagetian developmental levels for deciding the nature, level and complexity of the content while developing science textbooks at any grade. It is further recommended that teachers replace the didactic teaching method with the interactive one. The teachers should group students with different reasoning abilities within the class. Teachers should use different teaching techniques to introduce the content of the science textbooks to enhance, encourage and motivate students and to develop their attitude towards science learning.