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Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis.

ABSTRACT: Human pancreatic α-amylase (HPA), which works as a catalyst for carbohydrate hydrolysis, is one of the viable targets to control type 2 diabetes. The inhibition of α-amylase lowers blood glucose levels and helps to alleviate hyperglycemia complications. Herein, we systematically screened the potential HPA inhibitors from a library of natural products by molecular modeling. The modeling encompasses molecular docking, MM/GBSA binding energy calculations, MD simulations, and ADMET analysis. This research identified newboulaside B, newboulaside A, quercetin-3-O-β-glucoside, and sasastilboside A as the top four potential HPA inhibitors from the library of natural products, whose Glide docking scores and MM/GBSA binding energies range from -9.191 to -11.366 kcal/mol and -19.38 to -77.95 kcal/mol, respectively. Based on the simulation, among them, newboulaside B was found as the best HPA inhibitor. Throughout the simulation, with the deviation of 3Å (acarbose = 3Å), it interacted with ASP356, ASP300, ASP197, THR163, ARG161, ASP147, ALA106, and GLN63 via hydrogen bonding. Additionally, the comprehensive ADMET analysis revealed that it has good pharmacokinetic properties having not acutely toxic, moderately bioavailable, and non-inhibitor nature toward cytochrome P450. All the results suggest that newboulaside B might be a promising candidate for drug discovery against type 2 diabetes.

SUBMITTER: Basnet S

PROVIDER: S-EPMC10019617 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis.

Basnet Santosh S Ghimire Madhav Prasad MP Lamichhane Tika Ram TR Adhikari Rajendra R Adhikari Achyut A

PloS one 20230316 3

Human pancreatic α-amylase (HPA), which works as a catalyst for carbohydrate hydrolysis, is one of the viable targets to control type 2 diabetes. The inhibition of α-amylase lowers blood glucose levels and helps to alleviate hyperglycemia complications. Herein, we systematically screened the potential HPA inhibitors from a library of natural products by molecular modeling. The modeling encompasses molecular docking, MM/GBSA binding energy calculations, MD simulations, and ADMET analysis. This re ...[more]

PMID: 36928801

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Dataset Information

Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis.

Publications

Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis.

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