Research Projects
Research Projects
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Kratom Alkaloid Interactions with Membrane Lipid Bilayers and
the Key Blood-Brain Barrier Receptors
2022-Current
Kratom Alkaloid Interactions with Membrane Lipid Bilayers and
the Key Blood-Brain Barrier Receptors
2022-Current
Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has garnered interest as a potential alternative to classical opioids for pain management and mitigating withdrawal symptoms, primarily due to its major alkaloids, mitragynine, 7-hydroxymitragynine, and mitragynine pseudoindoxyl, which act on opioid receptors with a potentially improved safety profile. This study employed all-atom molecular dynamics simulations to provide the first fundamental insights into how these alkaloids interact with a model cell membrane, revealing their interactions with membrane lipid bilayers. These findings on membrane partitioning are crucial for understanding the pharmacokinetics of kratom alkaloids and could ultimately guide the rational design of safer and more effective therapeutics for pain management.
Publications
Mohd Zubri, Nur Syahirunelisa, et al. 2025. Interactions of kratom alkaloids–mitragynine, 7-hydroxymitragynine, and mitragynine pseudoindoxyl with lipid bilayers: a molecular dynamics study. International Journal of Pharmaceutical, Nutraceutical and Cosmetic Science (IJPNaCS) 8.1 (2025): 124-139. Link
In silico Binding Prediction of Mitragyna speciosa Alkaloids to Human Opioid Receptors
Nur Balqis Nasuha Norazizi, Nurul Suhada Abd Razak & Siti Azma Jusoh
MSBMB 2024 - https://zenodo.org/records/13325014
A Study of Mitragynine Interactions with DPPC Lipid Bilayer using Molecular Dynamics Simulations
Aiman Najmi Noor Khilman, Zafirah Liyana Abdullah and Siti Azma Jusoh
Final Year Project, Faculty of Pharmacy, Universiti Teknologi MARA 2023 - https://zenodo.org/records/8141633
Interactions of Mitragynine Pseudoindoxyl nteractions with DPPC Lipid Bilayer - A Study using Molecular Dynamics Simulations
Aiman Najmi Noor Khilman, Zafirah Liyana Abdullah and Siti Azma Jusoh
Final Year Project, Faculty of Pharmacy, Universiti Teknologi MARA 2023 - https://zenodo.org/records/8143203
Grad Student
Nur Syahirunelisa Mohd Zubri (2023-2025)
MSc Thesis: Molecular Interaction and Behavior of Kratom Alkaloids-Mitragynine, 7-hydroxymitragynine and Mitragynine pseudoindoxyl-in DPPC lipid bilayers: A Molecular Dynamics Simulation Study
Funding
Geran Inisiatif Penyelidikan (GIP), UiTM | Molecular Interactions of Alkaloids with Lipid Bilayers.
Molecular Interactions Between LDL Receptor and PCSK9 Variants
2022-Current
Molecular Interactions Between LDL Receptor and PCSK9 Variants
2022-Current
The low-density lipoprotein receptor (LDLR) plays a critical role in cholesterol homeostasis by mediating the clearance of LDL cholesterol from the bloodstream. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates this process by binding to LDLR and promoting its lysosomal degradation, thereby reducing the receptor's availability on the cell surface and increasing circulating LDL cholesterol levels. Dysregulation of this interaction, particularly through gain-of-function mutations in PCSK9, can lead to familial hypercholesterolemia and elevated cardiovascular risk. Understanding the molecular details of LDLR-PCSK9 binding is therefore essential for developing targeted therapies to manage cholesterol levels.
In this study, we employed molecular dynamics simulations to investigate the structural dynamics of the LDLR-PCSK9 complex, focusing on two novel PCSK9 variants—E498A and R499G—identified in Malaysian familial hypercholesterolemia patients. These findings provide mechanistic insights into how specific PCSK9 mutations may alter LDLR binding and function, highlighting the importance of structural dynamics in cholesterol regulation and the potential impact of genetic variants on disease pathology.
Publications
Structural dynamics of LDL receptor interactions with E498A and R499G variants of PCSK9
Nur Alya Amirah Azhar, Chua Yung An, Hapizah Nawawi and Siti Azma Jusoh
Journal of Molecular Modeling (2025) 31:161 (WoS/Scopus) - https://doi.org/10.1007/s00894-025-06380-1
Review on Structures and Variants of Familial Hypercholesterolemia (FH) Target Proteins
Nur Alya Amirah Azhar, Fazleen Haslinda Mohd Hatta, Chua Yung An, Hapizah Nawawi and Siti Azma Jusoh
Journal of Public Health and Pharmacy (Scopus)
Genetic Spectrum of Familial Hypercholesterolaemia in the Malaysian Community: Identification of Pathogenic Gene Variants Using Targeted Next-Generation Sequencing
AZ Razman et al. 2022. Int. J. Mol. Sci. 23 (12) 14971. (WoS/Scopus) Link
Grad Student
Nur Alya Amirah Azhar (2025-2027)
PhD Thesis: Impact on LDL Receptor Binding caused by E498A and R499G PCSK9 Mutants - A Validation using the Crispr-Cas9 Method.
Nur Alya Amirah Azhar (2022-2024)
MSc Thesis: Structural Dynamics of LDL Receptor and Interactions with E498A and R499G PCSK9 Mutants – Novel Variants of FH in Malaysian Patients
Funding
Fundamental Research Grant Scheme (FRGS) 2024-2027, Ministry of Higher Education Malaysia
Virtual Screening of SAR-CoV-2 Main Protease Inhibitors
2022-2024
Virtual Screening of SAR-CoV-2 Main Protease Inhibitors
2022-2024
The SARS-CoV-2 main protease (Mpro, or 3CLpro) is a cysteine protease encoded within the viral ORF1a/b, which autocatalytically cleaves itself from the pp1a/pp1ab polyproteins and subsequently processes 11 other conserved cleavage sites to liberate non-structural proteins essential for replication. Mpro functions as a homodimer, with each protomer featuring a substrate-binding pocket characterized by a catalytic dyad (Cys145-His41) that is highly conserved across sarbecoviruses. The absence of a human homolog with equivalent specificity and its indispensable role in the viral lifecycle establish Mpro as a premier antiviral target.The clinical success of covalent Mpro inhibitors such as nirmatrelvir validates the inhibition of this enzyme as a powerful therapeutic strategy.
In this study, we employ computational virtual screening to identify novel Mpro inhibitors, leveraging the precision of structure-based drug design to screen expansive libraries of natural compounds alongside approved drugs for repurposing. This dual-pronged approach aims to uncover both new chemical scaffolds from natural sources with potentially favorable toxicity profiles, as well as established drugs that could be rapidly redeployed, thereby accelerating the discovery of potent anti-SARS-CoV-2 therapeutics.
Publications
NA Amran et al 2024. In silico Binding and Interactions of Known Antivirals to the Dimer Pocket of the SARS-CoV-2 Main Protease. IJPNACS 7 (2) 44-58. Link
A Rozaini et al 2024. Higher Binding Affinities of Hopea Phytocompounds to the SARS-CoV-2 Main Protease Than Known Antivirals. JESTEC 19 (5) 1751- 1774. Link
Grad Students
Nur Aqasyah Amran (2022-2024)
MSc Thesis: Binding of Known Antivirals to the Dimer Pocket of the SAR-CoV-2 Main Protease - An Insight Based on Molecular Docking and Dynamics Simulations
Nur Hannani Ahmad Rozaini (2022-2024), (Main Supervisor: Dr Fatahiya Md Tap)
MSc Thesis: Binding of Hopea Phytocompounds to the SARS-CoV-2 Main Protease Than Known Antiviral
Funding
Dana UiTM Cawangan Selangor (DUCS) | Project: SARS-CoV-2 (COVID-19) Rational Drug Design Targeting the Main Protease Potential Allosteric Binding Sites.
Nuclear Hormone Receptor Family
2014-Current
Nuclear Hormone Receptor Family
2014-Current
The work focuses on the molecular dynamics (MD) simulations and docking methods to assist screening of large scale chemical compounds. The receptors are proteins from the family of nuclear hormone receptors, which currently the targets for more than 30% FDA approved drugs.
Publications
Hio K.T., Jusoh S.A. and Shirley W.I. Siu, 2018. Chaos-embedded particle swarm optimization approach for protein-ligand docking and virtual screening. Journal of Cheminformatics.
Akbar, R., Jusoh, S.A., Amaro, R.E. and Helms, V., 2017. ENRI: A tool for selecting structure‐based virtual screening target conformations. Chemical Biology & Drug Design. (Q2; IF 2.396)
Swift, R.V., Jusoh, S.A., Offutt, T.L., Li, E.S. and Amaro, R.E., 2016. Knowledge-Based Methods to Train and Optimize Virtual Screening Ensembles. Journal of Chemical Information and Modeling, 56(5), pp.830-842. (Q1; IF 3.760)
251st American Chemistry Society (ACS) National Meeting - Computers in Chemistry, San Diego - USA. March 13-17, 2016. Title: Molecular dynamics-generated ensemble structures improve virtual screening performance. Jusoh, S.A., Swift, R.V., and Amaro, R.E. (Oral Presentation).
251st American Chemistry Society (ACS) National Meeting - Computers in Chemistry, San Diego - USA. March 13-17, 2016. ENRI: Enriching Virtual Screening Through Machine Learning. Akbar, R., Jusoh, S.A., Amaro, R.E. and Helms, V. (Poster)
3rd Annual Postdoctoral Research Symposium, Aug 14- 2015. Enhance Performance of Virtual Screening using MD Ensembles. Jusoh, S.A., Swift, R.V., and Amaro, R.E. (Poster)
FYP Students
Nur Amira Nabila Jamat & Siti Azma Jusoh 2019, Poster Presentation. Molecular Dynamics Simulations Ensemble Structures Revealed A Potential New Ligand Binding Pocket for Estrogen Receptor-alpha Antagonist Drugs, 30th Intervarsity Biochemistry Seminar 2019, Notthingham Universiti Malaysia. (Oral Presenter)
M Alwee Fikri Abdullah Hassan and Siti Azma Jusoh, 2018. 2nd International Symposium of Bioinformatics (InSyB 2018), Perdana University, Serdang. (Poster)
Farah Najihah Isa'Ali & Siti Azma Jusoh, 2018. 2nd International Symposium of Bioinformatics (InSyB 2018), Perdana University, Serdang. (Best Oral Presenter).
Siti Zaidah Rosman and Siti Azma Jusoh. Molecular Interactions of Dioxin Derivatives with Human Estrogen Receptors. 28th Intervarsity Biochemistry Seminar, 13th May 2017, UCSI University, Kuala Lumpur.
(Oral Presenter/BPharm Thesis Project)
Nurdalilah Anis Hasim and Siti Azma Jusoh. Chemical Compounds From Sunscreen Products Potential Endocrine Disruptors, 28th Intervarsity Biochemistry Seminar, 13th May 2017, UCSI University, Kuala Lumpur.
(Oral Presenter/BPharm Thesis Project)
Nurul Hafizah Ahmad Kamal and Siti Azma Jusoh. Molecular Docking Studies of Bisphenol A (BPA) Interactions with Estrogen Receptors. 28th Intervarsity Biochemistry Seminar, 13th May 2017, UCSI University, Kuala Lumpur. (Poster/BPharm Thesis Project)
Funding
Universiti Teknologi MARA and KPM Funding for Postdoctoral Scholarship (2014-2016) in Rommie Amaro Lab, UCSD
Structural Studies on OTCase SNP Mutations
2014-2018
Structural Studies on OTCase SNP Mutations
2014-2018
The study of human mutation of OTC enzyme, which can cause OTCD disease. The disease can be fatal for newborn babies and neurological effects to other patients. The aim is to predict effects of a single mutation on the structure of the OTC enzyme using molecular docking and MD simulations.
Publications
Ali EZ., et al. 2018. Mutation Study of Malaysian Patients with Ornithine Transcarbamylase Deficiency: Clinical, Molecular, and Bioinformatics Analyses of Two Novel Missense Mutations of the OTC Gene. BioMed Research International.
Asian Congress on Biotechnology, Kuala Lumpur, Malaysia. Nov 15-19, 2015. Predicting Effect of Missense Mutations at Active Site in Ornithine Transcarbamylase (OTC) Gene: In-Silico Webservers and Molecular Docking Analysis. Ali, E. Z., Zakaria, Y., Mohd Radzi, M. A. and Jusoh, S. A. (Extended Abstract & Poster Presentation)
Graduated Student
Dr Erni Zuraida Ali (PhD), 2019
Project Title: Effect of Missense Mutations to the Structure and Functions of OTCase Studied using MD Simulations and Molecular Docking.
Funding
BESTARI Grant UiTM 2016-2018/MYR40K (Principal Investigator). Project: Single Nucleotide Polymorphism (SNP) Effects On The Otcase Structure & Functions.
Structural Dynamics Studies on Membrane Proteins
2009-2018
Structural Dynamics Studies on Membrane Proteins
2009-2018
Publications
Beck A, Speicher T, Stoerger C, Sell T, Dettmer V, Jusoh S. A., Abdulmughni A, Cavalié A, Philipp SE, Zhu MX, Helms V, 2013. Conserved gating elements in TRPC4 and TRPC5 channels. Journal of Biological Chemistry, 288(27):19471-83.
Chik, W.D.W., Mohamed, R., Majeed, A.B.A. and Jusoh, S.A., 2012. Sequence analysis and homology modeling of TRPV5 and TRPV6 channels. In Business, Engineering and Industrial Applications (ISBEIA), 2012 IEEE Symposium, pp. 342-346.
Graduated Student
Dr Wan Dalila Wan Chik (PhD), 2018
Project Title: MD Simulations of TRPC channel.
Funding
FRGS 2011-2013/MYR117K (Principal Investigator). Project: Modeling And Dynamics Of The Transient Receptor Potential (TRP) Channels.
ERGS 2012-2015/MYR142K (Principal Investigator). Project: Molecular Modelling And Docking Studies Of P-glycoprotein
Structural Studies on Envelope Glycoprotein of Flaviviridae Viruses
2011-2018
Structural Studies on Envelope Glycoprotein of Flaviviridae Viruses
2011-2018
Hepatitis C Virus
This project is a continuing study from the previous PhD project. The main aim is to build a complete model of E1-E2 heterodimer due to the high resolution structure is not yet available.
Dengue Virus
As dengue fever still has no specific treatment in Malaysia, we embarked on the dengue virus envelope glycoprotein study. The study aimed to build the model structure of the envelope proteins, to characterize the protein dynamics behavior in lipid bilayer, and to perform virtual screening of potential binding compounds.
Graduated Student
Dr Nurul Azira Ismail (PhD), 2018
Project Title: MD Simulations and Docking Studies of E and M Proteins of Dengue Virus
Publications
Ismail NA, Jusoh SA, 2016. Molecular Docking and Molecular Dynamics Simulation Studies to Predict Flavonoid Binding on the Surface of DENV2 E Protein. Interdisciplinary Sciences: Computational Life Sciences. 11:1-3. (Q2)
Akbar R, Jusoh SA. 2013. Stability, orientation and position preference of the stem region (residues 689-703) in Hepatitis C Virus (HCV) envelope glycoprotein E2: a molecular dynamics study. F1000Research, pp 2. (Q1)
Funding
Cluster Computing Grant UiTM 2012-2014/MYR60K (Principal Investigator), Project: Membrane Protein Folding: Folding Of Envelope Glycoproteins Form Flaviviridae Viruses.
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