Work

Novel glucokinase activators: A structure-based pharmacophore modeling, QSAR analysis, and molecular dynamics approach

Year: 2024

Type: article

Abstract: Glucokinase (GK) activators are promising candidates for type 2 diabetes treatment. This study utilized structure-based pharmacophore modeling and QSAR analysis to identify novel activators. Virtual screening of a 250,000-compound library yielded eight new candidates with significant in vitro activity (over 50% activation at 25 µg/mL) and diverse structures. Molecular dynamics simulations revealed a potential mechanism involving a transient loop flip in the GK allosteric site, aligning with known activator behavior. The leading candidate, NSC12516, displayed superior hydrogen bonding with key residues (compared to known activator MRK501) and potentially stronger binding affinity due to favorable energetics. These findings clear the way for developing potent and selective GK activators for type 2 diabetes.

Source: Pharmacia

DOI: 10.3897/pharmacia.71.e131072

Authors: Mansour Al-Sayed Ahmad, Belal O. Al-Najjar, Ashok Shakya

Institution: Al-Ahliyya Amman University

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $107