Docking and Molecular Dynamics Study to Identify Novel Phytobiologics from Dracaena trifasciata against Metabolic Reprogramming in Rheumatoid Arthritis

Abstract

Enhancement of glycolysis and glutaminolysis are the two most common modalities associated with metabolic reprogramming in rheumatoid arthritis (RA). This enhancement is concomitant to the upregulation of hexokinase 2 (HK2) and glutaminase 1 (GLS1). Hence, the current study was undertaken to identify potential phytobiological inhibitors against HK2 and GLS1, from Dracaena (Sansevieria) trifasciata, an indigenous ethnomedicinal plant found in Pakistan, using computational analysis. Phytobiologics from Dracaena trifasciata were assessed for their ability to co-inhibit HK2 and GLS1 via molecular docking and molecular dynamics simulations. The results underscored seven phytobiologics with promising binding affinities for both HK2 and GLS1. Molecular dynamics simulations further elucidated that all seven identified phytobiologics inhibited HK2 by forming stable complexes but only five amongst the seven had the potential to form stable complexes with GLS1 in real time, thereby implying the potential of co-inhibition for these five compounds. Compound 28MS exhibited an equally strong binding profile for both HK2 (−8.19 kcal/mol) and GLS1 (−8.99 kcal/mol). Furthermore, it exhibited a similar trend in stability during simulation for both targets. Our results serve as a primer for a more lucid understanding towards co-inhibition of HK2 and GLS1 using multiple computational approaches. The identified phytobiologics should undergo in-vitro and in-vivo validation to corroborate their therapeutic potential in RA.

A Review on Therapeutic Activities of Coriandrum sativum L for Rheumatoid Arthritis Remedy

“…Rheumatoid Arthritis (RA) is a prevalent autoimmune disease affecting humans, with a global predominance of approximately 1%. [1]. It is an inflammatory disease in which the immune system of the body attacks healthy cells by mistake causing painful swelling in the affected body parts [2].…”

Dual inhibition of glycolysis and glutaminolysis for synergistic therapy of rheumatoid arthritis

“…In our previous study [ 20 ], we discovered novel compounds with the potential of dual inhibition of key enzymes of glycolysis and glutaminolysis, i.e., HK2 and GLS. Computational assessment revealed that 28MS inhibits both target enzymes similarly.…”