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Drug Res (Stuttg) 2020; 70(05): 226-232
DOI: 10.1055/a-1138-8725
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Use of Graph Based Descriptors for Determination of Structural Features Causing Modulation of Fructose-1,6-Bisphosphatase

Ashwani Kumar
1   Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, India
,
Manisha,
Kiran Bagri
1   Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, India
,
Parvin Kumar
2   Department of Chemistry, Kurukshetra University, Kurukshetra, India
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 22. Januar 2020

accepted 09. März 2020

Publikationsdatum:
03. April 2020 (online)

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Abstract

Fructose-1,6-bisphosphatase performs a significant function in regulating the blood glucose level in type 2 diabetes by controlling the process gluconeogenesis. In this research work optimal descriptor (graph) based quantitative structural activity relationship studies of a set of 203 fructose-1,6-bisphosphatase has been performed with the help of Monte Carlo optimization. Distribution of compounds into different sets such as training set, invisible training set, calibration set and validation sets resulted in formation of splits. Statistical parameters obtained from quantitative structural activity relationship modeling were good for various designed splits. The statistical parameters such as R2 and Q2 for calibration and validation sets of best split developed were found to be 0.8338, 0.7908 & 0.7920 and 0.7036 respectively. Based on the results obtained for correlation weights, different structural attributes were described as promoters and demoters of the endpoint. Further these structural attributes were used in designing of new fructose-1,6-bisphosphatase inhibitors and molecular docking study was accomplished for the determination of interactions of designed molecules with the enzyme.

Key words

Fructose-1,6-bisphosphatase inhibitors - QSAR - Monte Carlo method - Docking.

Supporting Information

 

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