Article
Biology
Payal Dhar, Fahmin Basher, Zhe Ji, Lei Huang, Si Qin, Derek A. Wainwright, Jerid Robinson, Shaye Hagler, Jing Zhou, Sean MacKay, Jennifer D. Wu
Summary: Research shows that tumor-derived NKG2D ligand soluble MIC can reprogram NK cells and provides a rationale for targeting sMIC to enhance the efficacy of current NK cell-based cancer immunotherapies.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemical Research Methods
Ting-Ting Ding, Ya-Ya Liu, Li-Ming Zhang, Jia-Rui Shi, Wei-Ren Xu, Shao-Yong Li, Xian-Chao Cheng
Summary: This study utilized pharmacophore modeling and molecular dynamics simulation to screen and obtain 9 new PPAR alpha/gamma agonists.
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
(2022)
Article
Biochemistry & Molecular Biology
Ma'mon M. Hatmal, Omar Abuyaman, Mutasem Taha
Summary: In this study, the use of multiple docked poses for machine learning-based QSAR modelling was introduced to discover potential inhibitors of the serine protease enzyme TMPRSS2. Xgboost, SVM, and RF were found to be the best machine learners with testing set accuracies reaching 90%. Three potential hits were identified by scanning known untested FDA approved drugs against TMPRSS2. Subsequent molecular dynamics simulation and covalent docking supported the new computational approach's results.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Immunology
Ritesh Kumar, Arianne L. Theiss, K. Venuprasad
Summary: ROR gamma t plays a crucial role in regulating IL-17-driven inflammation through multiple post-translational modifications. Understanding these pathways is essential for studying the pathogenic role of ROR gamma t+IL-17+ cells and developing potential therapeutic strategies.
TRENDS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Quentin Verron, Elin Forslund, Ludwig Brandt, Mattias Leino, Thomas W. Frisk, Per E. Olofsson, Bjorn Onfelt
Summary: The spatial distribution of activating ligands influences the formation and outcome of NK cell synapses. A combination of LFA-1 and CD16 engagement is necessary for mature synapses and degranulation. The organization of ligands in the synapse also affects its characteristics.
Article
Biochemistry & Molecular Biology
Long Li, Bernd Henning Stumpf, Ana-Suncana Smith
Summary: This study reveals that differences in affinity and length of proteins involved in membrane-mediated cell adhesion result in characteristic features in calculated phase diagrams. Additionally, stable nanodomains and ring-like patterns can spontaneously appear during cell experiments. Considering the role of the membrane allows for the recovery of experimentally observed patterns.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
J. Porter Hunt, Tyler J. Free, Jackelyn Galiardi, Kevin M. Watt, David W. Wood, Bradley C. Bundy
Summary: Thyroid receptor signaling plays a crucial role in physiological processes and its disruption can lead to severe disorders. Detection of thyroid receptor ligands is important for toxicology and pharmacology. A biosensor system was developed using cell-free protein synthesis and reengineered with different reporter systems, reducing the cost by 60%. This could potentially be a promising platform for high throughput screening and portable detection of human thyroid receptor ligands.
Article
Biochemistry & Molecular Biology
Sumera Zaib, Nehal Rana, Hafiz Saqib Ali, Nadia Hussain, Hanan A. Areeba, Hanan A. Ogaly, Fatimah A. M. Al-Zahrani, Imtiaz Khan
Summary: This study focuses on identifying drug molecules for the treatment of COVID-19 by targeting human proteases. By inhibiting specific protein targets associated with the SARS-CoV-2 virus, the entry and pathogenesis of the infectious agent can be obstructed.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Chemistry, Multidisciplinary
Minsun Kim, Hyesung Jo, Gyoo Yeol Jung, Seung Soo Oh
Summary: As biomolecules essential for sustaining life, proteins are unique and highly valuable for biomedical and biocatalytic applications due to their molecular recognition functions. Proteomimetic materials, including peptides, supramolecules, and inorganic molecules, mimic proteins and perform molecular recognition, expanding their potential bio-applications. This review focuses on proteomimetic designs derived from various materials and their conformations, providing insights for the development of advanced protein mimicry.
ADVANCED MATERIALS
(2023)
Article
Medicine, General & Internal
Saki Sultana, Geraint Berger, Christian Lehmann
Summary: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with unknown etiology and limited treatment options. Modulating the endogenous cannabinoid system (ECS) has shown benefits in alleviating pain and inflammation associated with IC/BPS.
Article
Biochemistry & Molecular Biology
Amalia Stefaniu, Lucia Camelia Pirvu
Summary: Fifty phytocompounds from different subclasses of polyphenols were analyzed using computational methods to evaluate their oral availability and bioactivity. The study confirmed the high bioavailability of soy isoflavones and the better bioavailability of free aglycones compared to their esterified and glycosylated forms. Analysis of bioactivity scores revealed the inhibitory potency of phenolic derivatives on cell modulators and the similarity within the flavonoid series. Supplementation with digestive enzymes is necessary for individuals with low digestive efficiency to obtain the health benefits of polyphenols.
Article
Chemistry, Multidisciplinary
Basudeb Mondal, Tahiti Dutta, Abinash Padhy, Sabyasachi Das, Sayam Sen Gupta
Summary: This review discusses lysosomes and their impact on diseases, as well as strategies and therapeutic applications of synthesizing peptides/chimeric molecules. It also introduces the use of lysosome-targeting nanocarriers for molecular delivery and the development of chimeric architectures with cell-specific degradation capabilities.
Article
Biochemistry & Molecular Biology
Daniela A. Covino, Maria G. Desimio, Margherita Doria
Summary: This study explores the potential strategies for clearing latent HIV reservoirs by using combinations of different latency-reversing agents (LRAs), with a focus on investigating the possibility of enhancing NK cell-mediated viral suppression through 2-LRA combinations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Trong Duc Le, Tien Cong Nguyen, Thi My Nuong Bui, Thi Kim Dung Hoang, Quoc Trung Vu, Chien Thang Pham, Chau Phi Dinh, Jibril Abdullahi Alhaji, Luc Van Meervelt
Summary: A series of novel N-aryl 2-{[5-(naphthalen-1-ylmethyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio}-N- phenylacetamide derivatives were synthesized and characterized. These compounds showed good inhibition activity against alpha-glucosidase, with compound 5b being the most potent inhibitor. Molecular docking studies revealed the interactions between these compounds and the active site of the enzyme.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Mays Alwash, Jean Gariepy
Summary: BirA* constructs can nonspecifically label proteins and identify intracellular protein interactors. Recombinant Affibody.BirA* constructs can be used to label and detect cell surface receptors.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Omar Abuyaman, Ma'mon M. Hatmal, Nawal Hijjawi, Ahmad A. Deeb, Mohammad Abuothman, Mutasem Taha
Summary: This study predicts the effect of TC missense mutations/SNPs on binding affinity to B12 and characterizes their contacts to B12 at the structural level. Results show that several missense SNPs have a neutral effect on B12 binding, while 17 amino acid locations were found to destabilize TC-B12 binding upon mutation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Mahmoud A. Al-Sha'er, Haneen A. Basheer, Mutasem O. Taha
Summary: Serine/threonine-protein kinase N2 (PKN2) plays important roles in cell cycle progression, migration, adhesion, and transcription activation signaling processes, as well as in cancer cell migration, invasion, and apoptosis. In this study, a QSAR-guided selection of docking-based pharmacophores approach was used to model PKN2 as a potential therapeutic target for cancer. Several pharmacophores were extracted from docked ligand poses and used to screen for new anti-PKN2 leads. Three promising compounds with low micromolar IC50 values were identified and showed cytotoxic properties against cancer cells in pharmacological assays.
MOLECULAR DIVERSITY
(2023)
Article
Immunology
Ma'mon M. Hatmal, Mohammad A. Al-Hatamleh, Amin N. Olaimat, Rohimah Mohamud, Mirna Fawaz, Elham T. Kateeb, Omar K. Alkhairy, Reema Tayyem, Mohamed Lounis, Marwan Al-Raeei, Rasheed K. Dana, Hamzeh J. Al-Ameer, Mutasem O. Taha, Khalid M. Bindayna
Summary: This study assessed the attitudes and side effects of Arab communities after receiving a COVID-19 vaccine and used machine learning tools to predict post-vaccination side effects based on predisposing factors. Vaccine hesitancy was reported among participants, and certain predisposing factors were found to be important in predicting side effects.
Review
Biochemistry & Molecular Biology
Ma'mon M. Hatmal, Mohammad A. I. Al-Hatamleh, Amin N. Olaimat, Walhan Alshaer, Hanan Hasan, Khaled A. Albakri, Enas Alkhafaji, Nada N. Issa, Murad A. Al-Holy, Salim M. Abderrahman, Atiyeh M. Abdallah, Rohimah Mohamud
Summary: Human breast milk contains not only nutritional components but also abundant microRNAs, which can impact epigenetic mechanisms and regulate immune and physiological functions. Studying the microRNA composition of human breast milk is important for improving nutrition during pregnancy and infancy and preventing future diseases.
Article
Chemistry, Medicinal
Alaa Abudayah, Safa Daoud, Mahmoud A. Al-Sha'er, Mutasem Omar Taha
Summary: This study proposes a method for extracting pharmacophores for activity cliffs-infested targets from molecular dynamics simulations and compares it with established ligand-based and structure-based methods. Using kinase inserts domain receptor as a case study, the results show that the pharmacophores based on molecular dynamics perform comparably to ligand-based and structure-based ones.
MOLECULAR INFORMATICS
(2022)
Article
Chemistry, Medicinal
Muhammad Ashram, Almeqdad Y. Habashneh, Sanaa Bardaweel, Mutasem O. Taha
Summary: A series of novel 1,2,3-triazole-benzoxazepine hybrid molecules were synthesized and evaluated for their anticancer properties. Three compounds showed excellent anticancer properties with micromolar IC50 values against the oncogenic kinase FLT3.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Chemistry, Medicinal
Dania Alkabbani, Lina A. Dahabiyeh, Mutasem O. Taha
Summary: Monoglyceride lipase (MGL) is a critical enzyme in lipolysis and the release of free fatty acids, and its inhibition by dipeptidyl peptidase-IV (DPP-IV) inhibitors provides a novel mechanism for improving insulin sensitivity and suppressing inflammation response. In this study, 6 known DPP-IV inhibitors were evaluated as potential MGL blockers, and all compounds showed successful docking into the catalytic site of MGL. Some of the inhibitors exhibited significant anti-MGL inhibitory effects, with gosogliptin and saxagliptin being the most potent inhibitors. This finding suggests a new therapeutic target for DPP-IV inhibitors beyond their traditional role in incretin hormones pathway.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Nour Jamal Jaradat, Walhan Alshaer, Mamon Hatmal, Mutasem Omar Taha
Summary: STAT3 is a vital transcription factor that is present in high levels in various types of cancer. Inhibition of STAT3 is considered a promising anti-cancer strategy. This study used multiple docked poses of STAT3 inhibitors to enhance machine learning QSAR modeling and identified critical descriptors for anti-STAT3 bioactivity. Two successful pharmacophores were generated and tested against a cancer database, resulting in the discovery of three novel compounds with potent anti-STAT3 effects. The findings highlight the potential of data augmentation in machine learning models for compound discrimination.
Article
Chemistry, Medicinal
Mahmoud A. Al-Sha'er, Mutasem Taha, Mahmoud A. Alelaimat
Summary: PI3K delta signaling is involved in cancer proliferation. In this study, we collected 79 known PI3K delta inhibitors and used them for pharmacophore modeling. Two optimal orthogonal pharmacophores were identified and evaluated using ROC curve analysis. These pharmacophores were then used to search for new anti-PI3K delta hits in the NCI chemical list. In vitro evaluation of the identified compounds showed potential anti-cancer activity, with the most potent hit exhibiting an IC50 value of 4.1 mu M against PI3K delta.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Chemistry, Medicinal
Amenah M. AL-Imam, Safa Daoud, Ma'mon M. Hatmal, Mutasem Omar Taha
Summary: This study used multiple docked poses of TTK inhibitors to augment training data for machine learning QSAR modeling. Critical descriptors for predicting anti-TTK bioactivity and for pharmacophore generation were determined, and three successful pharmacophores were deduced. These pharmacophores were then used for in silico screening against the NCI database, resulting in the evaluation of 14 hits with one compound showing reasonable dose-response curve and experimental IC50 of 1.0μM.
MOLECULAR INFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Nour Jamal Jaradat, Mamon Hatmal, Dana Alqudah, Mutasem Omar Taha
Summary: STAT3 is a transcription factor that has a significant role in activating gene transcription and is detected in different types of cancer. Inhibition of STAT3 is considered a potential anti-cancer strategy. However, the binding of STAT3 inhibitors to the shallow SH2 domain is complicated by hydration water molecules. To address this, this study proposes a method to extract pharmacophores from molecular dynamics (MD) simulations and employs genetic function algorithm coupled with machine learning (GFA-ML) to explore optimal combinations of pharmacophores for inhibitors. By screening a database, a low micromolar inhibitor with likely binding to the SH2 domain of STAT3 was identified.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2023)
Article
Pharmacology & Pharmacy
Isra Dmour, Mutasem O. Taha
Summary: Mechanochemistry involves the application of mechanical force to induce chemical changes in the material solid state. In this study, chitosan (CS) was grafted with 2,4-dichlorophenoxyacetic acid (2,4-D) to promote CO2 adsorption. The resulting tablets showed increased tensile strength, sustained drug release, and resistance to disintegration.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Chemistry, Medicinal
Safa Daoud, Shada J. Alabed, Sanaa K. Bardaweel, Mutasem O. Taha
Summary: The study reports pharmacophore models extracted from crystallographic complexes of potent ligands bound to MELK protein. these models were evaluated by ROC analysis and used to screen for inhibitors. Six potent anti-MELK hits were identified, with the most active hit showing an IC50 of 134.6 nM, and these inhibitors significantly inhibited the growth of cancer cells.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Review
Pathology
Iman Aolymat, Ma'mon M. Hatmal, Amin N. Olaimat
Summary: Cells use the heat shock response to activate heat shock proteins (HSPs), which play a critical role in maintaining protein balance and protecting cells from stress. Recent research has shown the involvement of HSPs and the heat shock factor 1 (HSF1) in a type of cell death called ferroptosis, which is characterized by altered oxidative status and lipid peroxidation. Understanding the regulation of HSF1 and HSPs in ferroptosis can lead to therapeutic interventions for various pathological conditions.