Computational Design and Docking-Based Analysis of IMP- 1088 Derivatives as NMT Inhibitors
Faculty Mentor
Raed Khashan
Major/Area of Research
Pharmacology (Pharmacology and Toxcology)
Description
INTRODUCTION: IMP-1088 is a potent and selective inhibitor of N-myristoyltransferases (NMT1 and NMT2), enzymes that catalyze the myristoylation of proteins essential for cellular signaling, pathogen survival, and disease progression. Given its therapeutic significance, optimizing the structure of IMP-1088 to enhance its efficacy and pharmacokinetic properties is crucial. This study focuses on the structure-activity relationship (SAR) of IMP-1088 by designing and analyzing ten novel molecules with strategic fluorine (F) modifications along with other elements, altering both the position and number of the atoms. Fluorine substitutions are known to influence drug-likeness, metabolic stability, and molecular interactions, making them a valuable approach in drug design.
METHOD: This research is a docking-based computational study that utilizes various molecular modeling tools, including MGL Tools, AutoDock Vina, PyMOL, and MolView. Through molecular docking simulations, this study assesses the binding affinity of each modified IMP-1088 analog to NMT1 and NMT2, determining how fluorine alterations impact interaction stability within the active site. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions will be performed to evaluate pharmacokinetic properties and potential off-target effects. The integration of docking studies with structural visualization and computational analyses will provide deeper insights into the molecular mechanisms governing NMT inhibition.
CONCLUSION: By leveraging advanced computational techniques, this research aims to contribute to the rational design of next-generation NMT inhibitors with improved selectivity, bioavailability, and therapeutic potential. The findings from this study may serve as a foundation for further experimental validation and drug development efforts in targeting NMT-related diseases.
Computational Design and Docking-Based Analysis of IMP- 1088 Derivatives as NMT Inhibitors
INTRODUCTION: IMP-1088 is a potent and selective inhibitor of N-myristoyltransferases (NMT1 and NMT2), enzymes that catalyze the myristoylation of proteins essential for cellular signaling, pathogen survival, and disease progression. Given its therapeutic significance, optimizing the structure of IMP-1088 to enhance its efficacy and pharmacokinetic properties is crucial. This study focuses on the structure-activity relationship (SAR) of IMP-1088 by designing and analyzing ten novel molecules with strategic fluorine (F) modifications along with other elements, altering both the position and number of the atoms. Fluorine substitutions are known to influence drug-likeness, metabolic stability, and molecular interactions, making them a valuable approach in drug design.
METHOD: This research is a docking-based computational study that utilizes various molecular modeling tools, including MGL Tools, AutoDock Vina, PyMOL, and MolView. Through molecular docking simulations, this study assesses the binding affinity of each modified IMP-1088 analog to NMT1 and NMT2, determining how fluorine alterations impact interaction stability within the active site. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions will be performed to evaluate pharmacokinetic properties and potential off-target effects. The integration of docking studies with structural visualization and computational analyses will provide deeper insights into the molecular mechanisms governing NMT inhibition.
CONCLUSION: By leveraging advanced computational techniques, this research aims to contribute to the rational design of next-generation NMT inhibitors with improved selectivity, bioavailability, and therapeutic potential. The findings from this study may serve as a foundation for further experimental validation and drug development efforts in targeting NMT-related diseases.