Molecular mechanics approaches for rational drug design: forcefields and solvation models

Bekono, Boris D.; Sona, Alfred N.; Eni, Donatus B.; Owono, L. C. Owono; Megnassan, Eugène; Ntie‐Kang, Fidele

doi:10.1515/psr-2019-0128

Cited by 3 publications

(2 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MMGBSA represents the summation of the different energy interactions otherwise called force fields (FFs) and this concept is widely used to predict in silico drug-target interactions. [51,52] Our Molecular Mechanics with Generalized Born Surface Area (MMGBSA) calculations revealed that the dominant factor responsible for the spontaneous and robust total binding energy of the complexes is the Van der Waals interaction (VDW). Based on the overall binding free energy values, it has become evident that Meliantrol and Tamarixetin represent the most effective inhibitors of HOS when compared to standard Inabenfide.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanics with Generalized Born Surface Area (MMGBSA) Calculations and Docking Studies Unravel some Antimalarial Compounds Using Heme O Synthase as Therapeutic Target

Adelusi,

Bolaji,

Ojo

et al. 2023

ChemistrySelect

View full text Add to dashboard Cite

The enzyme Heme O Synthase (HOS) is essential for producing heme A and heme O, which are critical for defense against reactive oxygen species, drug detoxification, gas synthesis, transport, and electron transport in Plasmodium species. It has become vital to discover inhibitory molecules/compounds/medicines that target the synthesis of heme due to the emergence of drug‐resistant strains of Plasmodium falciparum. Therefore, in this study, we employed molecular mechanics with Generalized Born surface area (MMGBSA) calculations and docking studies to investigate potential antimalarial compounds targeting HOS from antimalarial botanicals. Screening these compounds, we have identified 2 compounds; Meliantrol and Tamarixetin with better binding affinities (−8.4 Kcal/mol and −8.3 Kcal/mol respectively) than the current standard inhibitor(Inabenfide) of HOS (−8.0 Kcal/mol). The MMGBSA calculations provided insight into the thermodynamics of the binding process and helped identify key interactions responsible for the stability of the HOS‐ligand complex. In addition, the 2 compounds were further screened comparatively with the standard HOS inhibitor considering their protein‐ligand interaction profile and ADMET profile and these 2 selected compounds outperformed Inabenfide. Our results predict that these compounds are potential drug candidates with domiciled therapeutic functions against Malaria therefore, open doors for more experimental validations for drug development.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Mechanics with Generalized Born Surface Area (MMGBSA) Calculations and Docking Studies Unravel some Antimalarial Compounds Using Heme O Synthase as Therapeutic Target

Adelusi,

Bolaji,

Ojo

et al. 2023

ChemistrySelect

View full text Add to dashboard Cite

show abstract

“…Over the past decades, MM approach plays an important role in understanding the ligand-protein structures, interactions and optimizing leads. It is achieved by MM potential energy function, which represents the sum of different energy terms, referred as “force fields” [ 59 ]. MM potential energy functions are used in various sampling methods, such as MD and MC (Monte Carlo).…”

Section: Computational Biology In Drug Designmentioning

confidence: 99%

Application of Computational Biology and Artificial Intelligence in Drug Design

Zhang

Luo

et al. 2022

IJMS

View full text Add to dashboard Cite

Traditional drug design requires a great amount of research time and developmental expense. Booming computational approaches, including computational biology, computer-aided drug design, and artificial intelligence, have the potential to expedite the efficiency of drug discovery by minimizing the time and financial cost. In recent years, computational approaches are being widely used to improve the efficacy and effectiveness of drug discovery and pipeline, leading to the approval of plenty of new drugs for marketing. The present review emphasizes on the applications of these indispensable computational approaches in aiding target identification, lead discovery, and lead optimization. Some challenges of using these approaches for drug design are also discussed. Moreover, we propose a methodology for integrating various computational techniques into new drug discovery and design.

show abstract

Computational discovery of dual potential inhibitors of SARS‐CoV‐2 spike/ACE2 and Mpro: 3D-pharmacophore, docking-based virtual screening, quantum mechanics and molecular dynamics

Bekono,

Onguéné,

Simoben

et al. 2024

Eur Biophys J

View full text Add to dashboard Cite

Molecular mechanics approaches for rational drug design: forcefields and solvation models

Cited by 3 publications

References 64 publications

Molecular Mechanics with Generalized Born Surface Area (MMGBSA) Calculations and Docking Studies Unravel some Antimalarial Compounds Using Heme O Synthase as Therapeutic Target

Molecular Mechanics with Generalized Born Surface Area (MMGBSA) Calculations and Docking Studies Unravel some Antimalarial Compounds Using Heme O Synthase as Therapeutic Target

Application of Computational Biology and Artificial Intelligence in Drug Design

Computational discovery of dual potential inhibitors of SARS‐CoV‐2 spike/ACE2 and Mpro: 3D-pharmacophore, docking-based virtual screening, quantum mechanics and molecular dynamics

Contact Info

Product

Resources

About