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Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

3-D QSAR and protein-protein interaction studies on neuraminidase against Clostridium perfringens: An Approach towards target identification using structure based drug designing

The rapid onset of resistance to new drugs and emergence of antibiotic resistant bacteria has led to resurgence in life-threatening bacterial infections. These problems have revitalized interest in antibiotics and lead to new research. To gain further insight between structural and biological activity of Clostridium perfringens a gram positive, anaerobe, responsible for food poisoning, mynecrosis in wound infections and enterotoxemia in humans. We have considered various in silico approaches for developing new drug leads based on small ligand structure. The importance of neuraminidases in the virulence of C. perfringens makes it a potent target for the studies of drug designing against this microbe. Natural products or their direct derivatives play crucial roles in many diseases. In the present study, 3D QSAR analysis using kNN MFA method was performed on a series of pterocarpan derivatives as Clostridial neuraminidase inhibitors. Twenty five compounds using random selection and sphere exclusion method for the division of dataset into training and test set was chosen. KNN-MFA methodology with stepwise (SW), simulated annealing (SA) and genetic algorithm (GA) were used for model building and four predictive models have been generated. The most significant model have a high internal predictivity 64.80% (q2 = 0.6480) and external predictivity 95.46% (r2 =0.9546). Model showed that electrostatic and steric interactions play important role in determining neuraminidase inhibitory activity. The kNN-MFA plots provide further understanding of the relationship between structural features of substituted pterocarpan derivatives and their activities which were applied for designing new compounds as inhibitors. The drug likeliness of these compounds was checked through ADME property prediction and their interaction with the neuraminidase was checked by molecular docking studies. Moreover, analysis of protein-protein interaction network of NanI in C. perfringens was done.

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Pallavi Somvanshi 1
Suruchi Rai2
Bhartendu Nath Mishra2

1Department of Biotechnology
TERI University
10 Institutional Area
Vasant Kunj, New Delhi-110070, India
2Department of Biotechnology
Institute of Engineering and Technology
G.B. Technical University
Sitapur Road, Lucknow-226021, India

Ph: (91)11-26122222
Fx: (91)11-26122874
psomvanshi@gmail.com