Abstract
Background: Alzheimer disease (AD) can be considered as the most common age related neurodegenerative disorder and also an important cause of death in elderly patients. A number of studies showed the correlation of this disease pathology with BACE1 inhibitor and it is also evident that BACE1 inhibitor can function as a very potent strategy in treating AD.
Methods: In this present study, we aimed to prospect for novel plant-derived BACE1 inhibitors from Leea indica and to realise structural basis of their interactions and mechanisms using combined molecular docking and molecular dynamics based approaches. An extensive library of Leea indica plant derived molecule was compiled and computationally screened for inhibitory action against BACE1 by using virtual screening approaches. Furthermore, induced fit docking and classical molecular dynamics along with steered molecular dynamics simulations were employed to get insight of the binding mechanisms.
Results: Two triterpenoids, ursolic acid and lupeol were identified through virtual screening; wherein, lupeol showed better binding free energy in MM/GBSA, MM/PBSA and MM/GBVI approaches. Furthermore classical and steered dynamics revealed the favourable hydrophobic interactions between the lupeol and the residues of flap or catalytic dyadof BACE1; however, ursolic acid showed disfavorable interactions with the BACE1.
Conclusion: This study therefore unveiled the potent BACE1 inhibitor from a manually curated dataset of Leea indica molecules, which may provide a novel dimension of designing novel BACE1 inhibitors for AD therapy.
Keywords: BACE1, steered molecular dynamics, triterpenoids, Leea. indica, virtual screening, ursolic acid, Alzheimer disease.
Current Pharmaceutical Design
Title:Prospecting and Structural Insight into the Binding of Novel Plant-Derived Molecules of Leea indica as Inhibitors of BACE1
Volume: 24 Issue: 33
Author(s): S.M. Zahid Hosen*, Maruf Rubayed, Raju Dash, Md. Junaid, Sarmistha Mitra, Muhammad Shaiful Alam and Rupantar Dey
Affiliation:
- Molecular Modeling and Drug Design Laboratory, Pharmacology Research Division, Bangladesh Council of Scientific and Industrial Research, Chittagong-4220,Bangladesh
Keywords: BACE1, steered molecular dynamics, triterpenoids, Leea. indica, virtual screening, ursolic acid, Alzheimer disease.
Abstract: Background: Alzheimer disease (AD) can be considered as the most common age related neurodegenerative disorder and also an important cause of death in elderly patients. A number of studies showed the correlation of this disease pathology with BACE1 inhibitor and it is also evident that BACE1 inhibitor can function as a very potent strategy in treating AD.
Methods: In this present study, we aimed to prospect for novel plant-derived BACE1 inhibitors from Leea indica and to realise structural basis of their interactions and mechanisms using combined molecular docking and molecular dynamics based approaches. An extensive library of Leea indica plant derived molecule was compiled and computationally screened for inhibitory action against BACE1 by using virtual screening approaches. Furthermore, induced fit docking and classical molecular dynamics along with steered molecular dynamics simulations were employed to get insight of the binding mechanisms.
Results: Two triterpenoids, ursolic acid and lupeol were identified through virtual screening; wherein, lupeol showed better binding free energy in MM/GBSA, MM/PBSA and MM/GBVI approaches. Furthermore classical and steered dynamics revealed the favourable hydrophobic interactions between the lupeol and the residues of flap or catalytic dyadof BACE1; however, ursolic acid showed disfavorable interactions with the BACE1.
Conclusion: This study therefore unveiled the potent BACE1 inhibitor from a manually curated dataset of Leea indica molecules, which may provide a novel dimension of designing novel BACE1 inhibitors for AD therapy.
Export Options
About this article
Cite this article as:
Hosen Zahid S.M.*, Rubayed Maruf , Dash Raju , Junaid Md. , Mitra Sarmistha , Alam Shaiful Muhammad and Dey Rupantar , Prospecting and Structural Insight into the Binding of Novel Plant-Derived Molecules of Leea indica as Inhibitors of BACE1, Current Pharmaceutical Design 2018; 24 (33) . https://dx.doi.org/10.2174/1381612824666181106111020
DOI https://dx.doi.org/10.2174/1381612824666181106111020 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Role of Mitochondrial Genes in Neurodegenerative Disorders
Current Neuropharmacology Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer
Current Neurovascular Research New Approaches for the Selection and Evaluation of Anti-Prion Organic Compounds
Mini-Reviews in Medicinal Chemistry Synthesis of the Alzheimer Drug Posiphen into its Primary Metabolic Products (+)-N1-norPosiphen, (+)-N8-norPosiphen and (+)-N1, N8-bisnorPosiphen, their Inhibition of Amyloid Precursor Protein, α -Synuclein Synthesis, Interleukin-1β Release, and Cholinergic Action.
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Prediction of Disease-Related Genes Based on Hybrid Features
Current Proteomics Commentary (Research Highlights Utilizing Neuro-Inflammation: Turning Degeneration to Regeneration)
CNS & Neurological Disorders - Drug Targets The Many Neuroprogressive Actions of Tryptophan Catabolites (TRYCATs) that may be Associated with the Pathophysiology of Neuro-Immune Disorders
Current Pharmaceutical Design Peptide Inhibitors Targeting Protein Kinases
Current Pharmaceutical Design Molecular Modeling of an Orphan GPR18 Receptor
Letters in Drug Design & Discovery Polypeptide and Protein Aggregates with Neurotoxic Properties in Neurodegenerative Disorders: Emphasis on β-Amyloid-Induced Dysfunction of Receptor-Mediated Signal Transduction Pathways
Current Signal Transduction Therapy Pharmacologic Intervention in Axonal Excitability: In Vivo Assessment of Nodal Persistent Sodium Currents in Human Neuropathies
Current Molecular Pharmacology Bacteriophage - A Common Divergent Therapeutic Approach for Alzheimer's Disease and Type II Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets PCR/SSCP Detects Reliably and Efficiently DNA Sequence Variations in Large Scale Screening Projects
Combinatorial Chemistry & High Throughput Screening Dipeptidyl Peptidase-4 (CD26): Knowing the Function before Inhibiting the Enzyme
Current Medicinal Chemistry Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease
Current Alzheimer Research Focus on the Correlations between Alzheimer’s Disease and Type 2 Diabetes
Endocrine, Metabolic & Immune Disorders - Drug Targets The Effect of Single and Double Acetylation of Lysine Residues on Structural and Dynamical Features of Human Splicing Factor TDP-43 - A Statistical Ensemble Analysis
Combinatorial Chemistry & High Throughput Screening The Concept of Depression as a Dysfunction of the Immune System
Current Immunology Reviews (Discontinued) Organotypic Hippocampal Slice Cultures for Studies of Brain Damage, Neuroprotection and Neurorepair
Current Drug Targets - CNS & Neurological Disorders Enhancing Central Nervous System Endogenous GLP-1 Receptor Pathways for Intervention in Alzheimers Disease
Current Alzheimer Research