Journal of Biomolecular Structure & Dynamics

Complement C5 is the target of the monoclonal antibody eculizumab, used in complement dysregulating disorders, like the rare disease Paroxysmal Nocturnal Hemoglobinuria (PNH). PNH is an acquired hematopoietic stem cell condition characterized by aberrant destruction of erythrocytes, chronic hemolytic anemia, and thromboembolism propensity. C5 is a protein component of the complement system which is part of the immune system of the body and plays a prominent role in the destruction of red blood cells, misidentifying them as a threat...

The serine/threonine kinase (STK) plays a central role as the primary kinase in poxviruses, directing phosphoryl transfer reactions. Such reactions are pivotal for the activation of certain proteins during viral replication, assembly, and maturation. Therefore, targeting this key protein is anticipated to impede virus replication. In this work, a structural bioinformatics approach was employed to evaluate the potential of drug-like kinase inhibitors in binding to the ATP-binding pocket on the STK of the Mpox virus...

The COVID-19 pandemic caused by the SARS-CoV-2 virus, recognized by the World Health Organization (WHO), has led to 164,523,894 confirmed cases and 3,412,032 deaths globally as of May 20, 2021. SARS-CoV-2 encodes crucial proteases for its replication cycle, including the papain-like protease (PLpro), presenting a potential target for developing COVID-19 treatments. Mauritine, a cyclopeptide alkaloid found in the Ziziphus-spina christi plant, exhibits antiviral properties and was investigated for its affinity and toxicity towards PLpro using molecular docking through MGLTools 1...

AkT1, significantly impacts many tumours cell functions, like transcription, apoptosis, glucose metabolism, cell proliferation, and cell migration. For tumours to develop and spread, aberrant activation of AKT1 is essential. Therefore, a major focus of molecularly targeted PCa treatment is AKT1. The present study investigates the effect of piperine compared to SDF using in-vitro studies, viz colony formation assay, comet assay and AKT1 gene expression studies using human PCa cell line PC3. A cluster of approximately at least 50 cells constitutes a colony...

The objective of research was to examine the likely anticancer effectiveness of distinct pillar[5] arene derivatives, ws-penta-P[5] and ws-deca-P[5], on breast and lung cancer cell lines in vitro . To achieve this goal, breast cancer (MCF7) cells, lung cancer (A549) cells, healthy cells (HEK293) were utilized. The IC50 dose of ws-penta-P[5] and ws-deca-P[5] was determined using the MTT method. Both treatment (pillar[5] arene applied) and control (pillar[5] arene not applied) groups were established for all three cell lines...

The selective design of competitive enzyme inhibitors is an extremely difficult task but necessary work for certain types of systems, such as the phosphodiesterase (PDE) system addressed in this article. In the PDE family, PDE2A and PDE9 respectively target the central nervous system and heart failure, and share many conserved amino acids at their binding sites. Therefore, gaining a deep understanding of the selective mechanisms of PDE2A/9A is crucial for designing highly selective drugs. In this study, various computer-aided drug design (CADD) methods, including molecular docking, molecular dynamics simulations (MD), and binding free energy calculations, are employed to explore the selective mechanisms of PDE2A/9A...

The presence of HLA-DRB1 alleles that encode critical points associated with environmental interactions is associated with increased risk of rheumatoid arthritis caused by anti-citrullinated protein antibodies. Therefore, interleukin-6 (IL-6), a multifunctional cytokine that controls both local and systemic acute inflammatory responses through its ability to induce a phase response, plays a serious role. Its overexpression leads to pathological challenges such as rheumatoid arthritis and menopausal osteoporosis...

This work describes the successful synthesis of a series of three novel thiazolidinone-carvone-O-alkyl hybrids through a two-step approach involving heterocyclization and O-alkylation reactions. Comprehensive structural characterization of the obtained products was achieved using NMR and HRMS spectroscopic techniques. This study assessed in vitro antiproliferative activity of synthesized thiazolidinone-carvone-O-alkyl hybrids ( 5a-c ) against various human cancer cell lines, viz. HT-1080 (fibrosarcoma), A-549 (lung cancer), MCF-7 (breast cancer) and MDA-MB-231 (breast cancer)...

Gamma-aminobutyric acid (GABA) signaling is the principal inhibitory pathway in the central nervous system. It is critical in neuronal cell proliferation and fate determination. Any aberration in GABA inhibition results in psychiatric and neurological diseases. Thus, modulating GABAergic neurotransmission has become the basis of drug therapy for psychiatric and several neurological diseases. Though GABA and muscimol are classical inhibitors of GABA receptors, the search for novel inhibitors continues unabated...

Interleukin-6 (IL-6) is a cytokine that involved in the different phases of wound healing. It is responsible for promoting inflammation, regulating tissue repair scar formation, stimulating the production of extracellular matrix components and recruiting immune cells to the wound site. Therefore, suppressing IL-6 is beneficial for wound healing. However, no small molecules are currently available in the market against the IL-6. As a result, this research gap motivates us to find a potential inhibitor. This study aimed to investigate the wound healing potential of novel β-cycloidal-derived mono-carbonyl curcumin analogs reported in the literature through screening a series of computational studies...

Peptide-lipid interactions play an important role in maintaining the integrity and function of the cell membrane. Even slight changes in these interactions can induce the development of various diseases. Specifically, peptide misfolding and aggregation in the membrane is considered to be one of the triggers of Alzheimer's disease (AD), however its exact mechanism is still unclear. To this end, an increase of amyloid-beta (A β ) peptide concentration in the human brain is widely accepted to gradually produce cytotoxic A β aggregates (plaques)...

Spike glycoprotein has a significant role in the entry of SARS-CoV-2 to host cells, which makes it a potential drug target. Continued accumulation of non-synonymous mutations in the receptor binding domain of spike protein poses great challenges in identifying antiviral drugs targeting this protein. This study aims to identify potential entry inhibitors of SARS-CoV-2 using virtual screening and molecular dynamics (MD) simulations from three distinct chemical libraries including Pandemic Response Box, Drugbank and DrugCentral, comprising 6971 small molecules...

Cardiovascular diseases (CVDs) pose a significant global health threat, with familial hypercholesterolemia (FH) being a key genetic contributor. The apolipoprotein E (APOE) gene plays a vital role in lipid metabolism, and its variants are associated with CVD risk. This study explores prevalent APOE variants (p.R163C, p.R176C, p.R246C and p.V254E) using genetic and structural analyses. The research, initiated by identifying high-frequency APOE variants through the ABraOM database, utilizes homology modeling and molecular dynamics (MD) simulations to understand the structural consequences...

Dengue is a rapidly evolving arboviral disease that mainly affects tropical and subtropical regions of the world. The lack of therapeutic drugs and effective vaccines suggests that further resources need to be investigated. The effectiveness of the existing dengue vaccine is improbable as its efficacy depends on prior exposure to the dengue virus(DENV). Although the mechanism underlying the action of bioactive compounds to limit viral replication is less studied and still needs to be further explored, medicinal plants are excellent alternatives to combat DENV infection...

Cervical cancer poses a significant global health challenge, ranking as the fourth most common cancer among women worldwide and resulting in approximately 300,000 deaths yearly, predominantly caused by high-risk human papillomavirus strains (HPV), mainly types 16 and 18. The scenario poses the urgent need of the hour to develop effective treatment strategies that can address the complexity of cervical cancer and multitargeted inhibitor designing that holds promise as it can simultaneously target multiple proteins and pathways involved in its progression and have the potential to enhance treatment efficacy, reduce the likelihood of drug resistance...

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase...

The transforming growth factor beta (TGF- β ) signaling pathway is believed to play essential roles in several physiological activities, including cancer. TGF- β receptor type I (TBR-I) is a key membrane receptor protein in the TGF- β signaling pathway, which relates to many intracellular biological effects. In recent years, cold atmospheric plasma (CAP) has been found to have promising prospects in selective anticancer therapy and has confirmed its essential role in the TGF- β signaling pathway...

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Type 2 Diabetes Mellitus (T2DM), as a significant health concern globally, particularly in India, underscoring the vital need for effective therapeutics. Current drug therapies for T2DM may have limitations, leading researchers to explore natural products as alternatives. In this study. We have investigated the anti-diabetic compounds from the Costus genus, known as the insulin plant, which is abundant in southern India. The bioinformatics tools and software used for in-silico analysis to identify potential therapeutic compounds and hub genes associated with T2DM in the Indian population that could cut short the in-vitro and in-vivo experimental approaches in near future...

Clostridioides difficile infection (CDI) is a significant concern caused by widespread antibiotic use, resulting in diarrhea and inflammation from the gram-positive anaerobic bacterium C. difficile . Although bezlotoxumab (Bez), a monoclonal antibody (mAb), was developed to address CDI recurrences, the recurrence rate remains high, partly due to reduced neutralization efficiency against toxin B2. In this study, we aimed to enhance the binding of Bez to C. difficile toxin B2 by combining computational simulations and mutational analyses...