Journal of Biomolecular Structure & Dynamics最新文献_第10页

Microscopic effects of proline co-solvent on alanine homopeptide structure, solvation and helix folding dynamics. 脯氨酸共溶剂对丙氨酸同肽结构、溶剂化和螺旋折叠动力学的微观影响。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-12 DOI: 10.1080/07391102.2025.2500681

Krzysztof Kuczera, Robert Szoszkiewicz, Gouri S Jas

{"title":"Microscopic effects of proline co-solvent on alanine homopeptide structure, solvation and helix folding dynamics.","authors":"Krzysztof Kuczera, Robert Szoszkiewicz, Gouri S Jas","doi":"10.1080/07391102.2025.2500681","DOIUrl":"https://doi.org/10.1080/07391102.2025.2500681","url":null,"abstract":"We present a computational investigation to explore the influence of the protective osmolyte proline as a co-solvent on peptide structure and dynamics for a series of alanine-based peptides, (ALA)n of length n = 5, 8, 15, and 21 residues. Applying multi-microsecond molecular dynamics simulations in a 2 M proline solution, we evaluate peptide structure, solvation and helix folding dynamics and compare to behavior in pure water. Proline addition enhances helix content and significantly slows folding and unfolding times, correlating with a 1.9-fold increase in solvent viscosity. Notably, ALA15 helix content increases from 25% to 49% and relaxation time rises from 110 ns to 540 ns in proline relative to water. Microscopic solvation effects of proline include peptide compaction and dehydration, exclusion of proline from the backbone, formation of weak interactions with the ALA methyl sidechains, and strong interactions with water. The differences of these effects on the helix and coil states drive helix stabilization by proline. Low-dimensional kinetic modeling with Optimal Dimensionality Reduction predicts distinct folding mechanisms: shorter peptides (ALA5-ALA15) exhibit direct helix-coil transitions, and only the longest ALA21 follows a more complex folding pathway involving intermediates. Statistically, enhanced stability of hydrogen bonds in the peptide centers and strong correlation between transitions on neighboring residues are shared between water and proline solutions. However, there is a preference for helix initiation at the N-terminus under proline influence. Our analysis describes the molecular mechanisms of how proline modulates peptide behavior, offering atomistic insights into helix stabilization and folding mechanisms mediated by osmolytes.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunoinformatic approach for designing a multi-epitope vaccine against non-typhoidal salmonellosis using starvation-stress response proteins from Salmonella Oranienburg. 利用奥兰氏沙门氏菌饥饿应激反应蛋白设计非伤寒沙门氏菌多表位疫苗的免疫信息学方法

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-11 DOI: 10.1080/07391102.2025.2500685

Lennin Isaac Garrido-Palazuelos, Mamuna Mukhtar, Salman Ali Khan, José Andrés Medrano-Félix, Haris Ahmed-Khan, Fahad M Alshabrmi, Osvaldo López-Cuevas, Berenice González-Torres, Nohelia Castro-Del Campo, Cristóbal Chaidez, José Roberto Aguirre-Sánchez, Hailah M Almohaimeed

{"title":"Immunoinformatic approach for designing a multi-epitope vaccine against non-typhoidal salmonellosis using starvation-stress response proteins from Salmonella Oranienburg.","authors":"Lennin Isaac Garrido-Palazuelos, Mamuna Mukhtar, Salman Ali Khan, José Andrés Medrano-Félix, Haris Ahmed-Khan, Fahad M Alshabrmi, Osvaldo López-Cuevas, Berenice González-Torres, Nohelia Castro-Del Campo, Cristóbal Chaidez, José Roberto Aguirre-Sánchez, Hailah M Almohaimeed","doi":"10.1080/07391102.2025.2500685","DOIUrl":"https://doi.org/10.1080/07391102.2025.2500685","url":null,"abstract":"Non-typhoidal Salmonella is responsible for gastrointestinal illnesses worldwide. Therefore, it is important to implement effective therapeutic interventions for preventing these diseases. Vaccines have proven highly efficacious in the treatment and prevention of several illnesses. Nevertheless, there is currently no authorized vaccine available for non-typhoidal salmonellosis. This study aimed to employ in silico techniques to develop a multi-epitope vaccine targeting non-typhoidal salmonellosis. Specifically, we focused on proteins associated with the starvation stress response (SSR) in Salmonella Oranienburg. The presence of these proteins is essential for the survival and disease of the host organism. The vaccine sequence was constructed utilizing B-cell and T-cell epitopes. Linkers, adjuvants and PADRE sequences were used to establish connections between epitopes. The vaccine exhibited no allergenicity, toxigenicity and a significantly high antigenicity score. Docking analysis conducted between the designed vaccine and the TLR-1, TLR-2 and TLR-4 receptors demonstrated favorable interactions and the potential to activate these receptors. In addition, it was found through immunological simulation testing that the vaccine elicits a robust immune response. The use of these proteins in the construction of a multi-epitope vaccine shows potential in terms of both safety and immunogenicity.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational exploration of TITIN variations: insights from whole exome sequencing and molecular dynamics simulation study. TITIN变异的计算探索：来自全外显子组测序和分子动力学模拟研究的见解。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-11 DOI: 10.1080/07391102.2025.2500683

Amrita Mukhopadhyay, Bharti Devi, Anurag T K Baidya, Manohar Lal Yadav, Rajnish Kumar, Bhagyalaxmi Mohapatra

{"title":"Computational exploration of TITIN variations: insights from whole exome sequencing and molecular dynamics simulation study.","authors":"Amrita Mukhopadhyay, Bharti Devi, Anurag T K Baidya, Manohar Lal Yadav, Rajnish Kumar, Bhagyalaxmi Mohapatra","doi":"10.1080/07391102.2025.2500683","DOIUrl":"https://doi.org/10.1080/07391102.2025.2500683","url":null,"abstract":"Titin (TTN), the largest known human protein (∼4 MDa), is considered as a key component for sarcomere integrity and function. Mutations in the TTN gene play a pivotal role in the genetic underpinnings of Dilated Cardiomyopathy (DCM). In the present study, we have conducted whole exome sequencing (WES) on 15 patients (5 familial and 10 sporadic) diagnosed with idiopathic DCM and identified 88 exonic variants. Here, we also report for the first time four novel variants comprising two frame-shifts, one missense, and one stop-codon variant. These variants are predominantly located in the A-band region (39 variants) of TTN, a critical region for its mechanical stability and interaction with other sarcomeric proteins, followed by the I-band domain (33 variants), Z-disc domain (7 variants), and M-band region (9 variants). To discern the functional repercussions of these variations, we have performed several bioinformatics analyses including pathogenicity prediction, protein stability, and protein-protein docking followed by molecular dynamics (MD) simulations on both wild-type and mutant TTN fragments with their corresponding interacting partners. We reveal that variations in the A-band domain significantly alter the protein's structural dynamics, leading to decreased mechanical stability and altered protein-protein interactions. These changes are likely to disrupt sarcomere function, thereby elucidating their role in the pathogenesis of DCM.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating transcriptomics with disease-gene network and identification of EGFR kinase target: inhibitor discovery through virtual screening of natural compounds for brain cancer therapy. 整合转录组学与疾病基因网络和EGFR激酶靶点的鉴定：通过虚拟筛选天然化合物发现脑癌治疗抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-08 DOI: 10.1080/07391102.2025.2501672

Mohd Rehan, Wejdan M AlZahrani, Firoz Ahmed, Mohammad Imran Khan, Hifzur Rahman Ansari, Shazi Shakil, Moustafa E El-Araby, Salman Hosawi, Mohammad Saleem

{"title":"Integrating transcriptomics with disease-gene network and identification of EGFR kinase target: inhibitor discovery through virtual screening of natural compounds for brain cancer therapy.","authors":"Mohd Rehan, Wejdan M AlZahrani, Firoz Ahmed, Mohammad Imran Khan, Hifzur Rahman Ansari, Shazi Shakil, Moustafa E El-Araby, Salman Hosawi, Mohammad Saleem","doi":"10.1080/07391102.2025.2501672","DOIUrl":"https://doi.org/10.1080/07391102.2025.2501672","url":null,"abstract":"Brain cancer represents a highly aggressive malignant tumor with a challenging prognosis and limited treatment options. Employing advanced analytical methods, including Kinase Enrichment Analysis and Disease-Gene Network integration, the research identifies EGFR as a crucial therapeutic target for brain cancer. EGFR, a key player in cellular functions and elevated in various cancers, particularly brain cancer, is targeted using small molecule inhibitors like erlotinib and gefitinib. Despite promising results, challenges such as drug resistance and adverse effects necessitate exploration of alternative therapies. Natural compounds show significant potential for cancer with minimal associated toxicity. Thus, the natural compounds database was explored for EGFR kinase inhibitors. Utilizing molecular docking and dynamic simulation, our study identified five natural compounds-citicoline, silodosin, picroside I, canertinib, and tauroursodeoxycholic acid-as potential EGFR kinase inhibitors. Detailed exploration of their binding attributes, including pose, interacting residues, molecular interactions, dynamic behavior, and predicted binding energy, along with comparisons to the native inhibitor, underscored their potential. Notably, among the five natural compounds screened, canertinib is a known covalent inhibitor of EGFR kinase. However, its specific binding pose remains unexplored. Thus, to uncover the precise binding orientation, covalent docking simulation for canertinib was conducted. Additionally, it is noteworthy that all the five proposed compounds predicted to penetrate the blood-brain barrier, meeting the essential criteria for reaching brain. We anticipate that this study will provide valuable leads for experimental testing in the laboratory, advancing the prospects of brain cancer management.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel thiosemicarbazones of coumarin incorporated isatins: synthesis, structural characterization and antileishmanial activity. 香豆素中含有isatins的新型硫代氨基脲类化合物：合成、结构表征和抗利什曼原虫活性。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2498072

Saira Khatoon, Rabbia Asif, Saima Kalsoom, Aiman Aroosh, Arshad Islam, Syeda Sumayya Tariq, Zaheer Ul-Haq, Muhammad Moazzam Naseer

{"title":"Novel thiosemicarbazones of coumarin incorporated isatins: synthesis, structural characterization and antileishmanial activity.","authors":"Saira Khatoon, Rabbia Asif, Saima Kalsoom, Aiman Aroosh, Arshad Islam, Syeda Sumayya Tariq, Zaheer Ul-Haq, Muhammad Moazzam Naseer","doi":"10.1080/07391102.2025.2498072","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498072","url":null,"abstract":"Leishmaniasis, a neglected tropical disease affecting 0.7 to 1.3 million people annually, has only a few toxic therapeutic options. This study describes the synthesis, structural characterization, in silico and in vitro assessment of novel thiosemicarbazones of coumarin incorporated isatins (6a-6m) as highly as potent and safe antileishmanial agents. Molecular docking was initially used to determine the binding of these compounds to the active cavity of the target protein (Leishmanolysin gp63) of Leishmania (L.) tropica. Among all the docked compounds, three 6d, 6f and 6l showed high binding affinities due to strong H-bonds and hydrophobic π-interactions. Importantly, the in vitro investigations of thirteen synthesized compounds for antileishmanial activity against L. tropica promastigotes and axenic amastigotes, complemented the docking results. The compound 6d was found to be the most active of the series at micromolar concentrations both against promastigotes (IC50 = 2.985 μmol/L) and axenic amastigotes (IC50 = 13.46 μmol/L) in comparison to the tarter emetic (IC50 = 12.56 μmol/L) and amphotericin B (IC50 = 1.826 μmol/L), respectively. Significantly, all active compounds are much less toxic as compared to the positive control (Triton X-100) and, tartar emetic (TA) and amphotericin B when screened for their toxicity against human erythrocytes. To gain further insight into the interaction dynamics of our target protein on binding with compound 6d, molecular dynamic simulation was performed for a course of 100 ns for both the apo-protein and the protein-ligand complex. The results revealed consistent structural stability for the protein-ligand complex, aligning with characteristics seen in the apo-proteins.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational study of diol camptothecin drug delivery process using MPEG-1-based nanosome structure: molecular dynamics approach. 基于mpeg -1纳米体结构的二醇喜树碱药物传递过程的计算研究：分子动力学方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2500686

Maziar Bahreini, Arezoo Ghaffari

{"title":"Computational study of diol camptothecin drug delivery process using MPEG-1-based nanosome structure: molecular dynamics approach.","authors":"Maziar Bahreini, Arezoo Ghaffari","doi":"10.1080/07391102.2025.2500686","DOIUrl":"https://doi.org/10.1080/07391102.2025.2500686","url":null,"abstract":"In recent years, the drug delivery process has become important for effective treatments of various diseases. However, drug carrier design is a complex procedure and many of designed structures do not perform well. Nanostructures are promising systems for effective drug delivery process. Between nanostructures, nanosomes are effective vesicles of spherical shape that can be created from different self-assembled nanosize components. It is expected the appropriate design of nanosome-based samples, introduced a suitable drug carrier for clinical applications. In current research, we introduced macrophage-expressed gene (MPEG-1) protein-based nanosome performance in diol camptothecin (CPT(OH)2) drug delivery process in aqueous environment for the first time. The molecular dynamics (MD) method implemented for this purpose by using dreiding force field. Our MD simulations were performed two main phases. In the first phase, defined samples equilibrated at initial condition (T0 = 300 K and P0 = 1 bar). Then, drug delivery performance of equilibrated samples was reported. Computational outputs predicted atomic stability of samples in standard condition. This performance is conducted from kinetic and potential energies convergence in equilibrium phase. Also, drug delivery process was detected after 0.12 ns in aqueous environment. Numerically, drug delivery ratio reached to 66%. Furthermore, zeta potential converged to -2.20 mV after 100 ns. From these outputs, we concluded MPEG-1-based nanosome can be used in actual cases for drug delivery in clinical applications.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Catechins anti-diabetic actions are mediated via multiple receptors, a mechanism deduced via molecular docking and dynamic simulations. 儿茶素的抗糖尿病作用是通过多种受体介导的，这一机制是通过分子对接和动态模拟推断出来的。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2499671

Muhanad Salih, Mosab Yahya Alnour, Tarig Omer Ahmed, Ahmed H Arbab, Bashir A Yousef

{"title":"Catechins anti-diabetic actions are mediated via multiple receptors, a mechanism deduced via molecular docking and dynamic simulations.","authors":"Muhanad Salih, Mosab Yahya Alnour, Tarig Omer Ahmed, Ahmed H Arbab, Bashir A Yousef","doi":"10.1080/07391102.2025.2499671","DOIUrl":"https://doi.org/10.1080/07391102.2025.2499671","url":null,"abstract":"Diabetes mellitus is a growing burden that affects a large proportion of the population worldwide, with long-term complications that cause a devastating effect on the function of various organs. The currently available treatments lack optimum therapeutic goals, increasing the need for new drug discovery. Catechins are natural flavonoids that demonstrate anti-diabetic effects; however, catechin's mechanism of action remains unclear. This study was aimed to unleash the molecular mechanism behind the catechin's effect on blood glucose levels. For that, we explored the capability of some catechins to bind and interact with glucagon-like peptide-1 receptor-1, pancreatic ATP-sensitive potassium channel, dipeptidyl peptidase-4, and sodium-glucose transporter-2, which is essential for euglycemia, using molecular docking screening and dynamic simulations. The results showed that all the tested catechins are potential sodium-glucose transporter-2 inhibitors, a mechanism revealed for the first time, and glucagon-like peptide-1 receptor-1 agonists with various affinities to these receptors. Moreover, among these compounds, (-)-Epigallocatechin 3-O-gallate, (-)-Gallocatechin 3-O-gallate demonstrated the ability to act as an ATP-sensitive potassium channel inhibitor, and dipeptidyl peptidase-4 inhibitor in addition to the previously mentioned mechanisms. The discovery introduces (-)-gallocatechin 3-O-gallate and (-)-Epigallocatechin 3-O-gallate as a hot subject for research, as the compounds require further optimization to initiate further pre-clinical and clinical studies.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects and molecular mechanisms of the combination of Andrographis paniculata and Anredera cordifolia as an insulin sensitizer: in vitro, network pharmacology, molecular docking, and dynamics studies. 穿心莲与凤梨联合作为胰岛素增敏剂的作用及分子机制：体外、网络药理学、分子对接及动力学研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2499224

Frangky Sangande, Sri Ningsih, Kurnia Agustini, Siska Andrina Kusumastuti, Nuralih Nuralih, Adam Arditya Fajriawan, Michael Chandra, Syofi Rosmalawati, Aiyi Asnawi, Krisyanti Budipramana

{"title":"Effects and molecular mechanisms of the combination of Andrographis paniculata and Anredera cordifolia as an insulin sensitizer: in vitro, network pharmacology, molecular docking, and dynamics studies.","authors":"Frangky Sangande, Sri Ningsih, Kurnia Agustini, Siska Andrina Kusumastuti, Nuralih Nuralih, Adam Arditya Fajriawan, Michael Chandra, Syofi Rosmalawati, Aiyi Asnawi, Krisyanti Budipramana","doi":"10.1080/07391102.2025.2499224","DOIUrl":"https://doi.org/10.1080/07391102.2025.2499224","url":null,"abstract":"Due to the complex mechanism of insulin resistance (IR), multi-component herbal medicines might be an alternative approach in the treatment of IR-related diseases, such as type 2 diabetes mellitus (T2DM). Andrographis paniculata (AP) and Anredera cordifolia (AC) have been reported to have anti-diabetic effects. However, their effect and mechanism of action in a mixed formula (FAPAC), especially as an insulin sensitizer have not been reported. Therefore, in vitro studies were performed to investigate the effect of FAPAC, and the molecular mechanisms were predicted by in silico studies through network pharmacology, molecular docking, and dynamics simulations. In vitro studies demonstrated that FAPAC at 2 µg/mL was comparable to metformin in increasing glucose uptake in IR-HepG2 cells. KEGG analysis revealed that IR was the top pathway and predicted that FAPAC acts as an insulin-sensitizing agent by inhibiting three main targets: IKBKB, PRKCD, and PTPN1. Consensus docking suggested 7-O-methyl wogonin, ninandrographolide, and 3-O-β-D-glucopyranosyl andrographolide as the potent inhibitors for IKBKB, PRKCD, and PTPN1, respectively. Furthermore, molecular dynamics confirmed that the potential compounds remained in the binding pocket throughout the simulation and had a good affinity toward their respective targets, comparable to native ligands.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of erectile dysfunction-related enzymes by ginger (Zingiber officinale)-derived compounds: molecular docking and dynamics studies. 生姜（Zingiber officinale）衍生化合物对勃起功能障碍相关酶的抑制：分子对接和动力学研究

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2502153

Ayodeji Osmund Falade, Kayode Ezekiel Adewole, Gideon Ampoma Gyebi, Ibrahim M Ibrahim, Kolawole Ayodapo Olofinsan

{"title":"Inhibition of erectile dysfunction-related enzymes by ginger (Zingiber officinale)-derived compounds: molecular docking and dynamics studies.","authors":"Ayodeji Osmund Falade, Kayode Ezekiel Adewole, Gideon Ampoma Gyebi, Ibrahim M Ibrahim, Kolawole Ayodapo Olofinsan","doi":"10.1080/07391102.2025.2502153","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502153","url":null,"abstract":"Erectile dysfunction (ED) is one of the common forms of sexual disorder that significantly impacts the psychosocial quality of life amongst male folks. Previous studies have evidenced the role of arginase-1 (Arg-1), angiotensin-I-converting enzyme (ACE), phosphodiesterase-5 (PDE-5) and acetylcholinesterase (AChE) in the progression of this pathology. In the current investigation, a library of compounds present in Zingiber officinale was screened to discover lead therapeutic agents for potential inhibitors of these metabolic enzymes. The compounds were subjected to molecular docking analysis with the various proteins' standard inhibitors. Subsequently, the thermodynamic stability of the protein-ligand complexes of two top-docked compounds with the highest binding affinities for each protein was studied further via molecular dynamics (MD) using the CHARMM-GUI website. Moreover, the Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) pharmacological properties and drug-likeness of the top-docked 5 compounds from the plant were investigated with the SuperPred and the SwissADME web servers. From the compounds' library, diacetoxy-6-gingerdiol, 10-gingerdione, alloaromadendrene, valencene, and 6-gingerdiol showed the strongest inhibitory capacities with the amino acids present at the catalytic pocket of the selected proteins. Nonetheless, valencene and alloaromadendrene displayed better stability with the various protein complexes. Given that all these compounds were predicted to be non-toxic and have acceptable drug-likeness profiles, this investigation revealed their potential as a source of lead phytochemicals from regularly consumed food substances to mitigate the pathophysiology of erectile dysfunction. However, additional lab-based experiments are required before these phytochemicals can be developed into clinically approved commercially available drugs.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational structure-guided approach to simulate delamanid and pretomanid binding to mycobacterial F420 redox cycling proteins: identification of key determinants of resistance. 计算结构引导方法模拟delamanid和pretomanid与分枝杆菌F420氧化还原循环蛋白的结合：鉴定耐药性的关键决定因素。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2498621

Gourav Chakraborty, Mahima Sudhir Kolpe, I V Ambily Nath, Avlokita Tiwari, Praapti Jayaswal, Niladri Patra

{"title":"Computational structure-guided approach to simulate delamanid and pretomanid binding to mycobacterial F420 redox cycling proteins: identification of key determinants of resistance.","authors":"Gourav Chakraborty, Mahima Sudhir Kolpe, I V Ambily Nath, Avlokita Tiwari, Praapti Jayaswal, Niladri Patra","doi":"10.1080/07391102.2025.2498621","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498621","url":null,"abstract":"The recently approved delamanid (DLM) and pretomanid (PTM) improved the existing options to treat multidrug-resistant tuberculosis (MDR-TB). However, the high spontaneous mutation rates in mycobacterial F420 genes ddn, fgd1, fbiA, fbiB, fbiC, and fbiD create a bottleneck to successful anti-TB treatments. Of known mutations, identifying the therapeutically relevant ones is a prerequisite for understanding the drug resistance mechanism. Here, we applied a multistep computational pipeline to rank the mutations in F420 genes associated with DLM/PTM resistance. The DLM-/PTM-resistant protein mutants were built and simulated their innate sensitivity towards the drugs. The molecular dynamics (MD) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations quantified the effect of key mutations on drug union. The dynamic cross-correlated map (DCCM) and principal component analysis (PCA) showed a substantial link between the drug binding region and other sections in the mutants, hints to their potential role as an allosteric site. Also, the alterations induced conformationally unstable proteins with decreased DLM/PTM affinity. These investigations highlighted the DLM-tolerant G53D and Y65S and PTM-resilient Y133M (Ddn), L308P (FbiA), and C562W (FbiC) as candidate loss-of-function mutants of progressive research. The present results and interpretations could supply vital clues for protein engineering and drug development.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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