In silico pharmacology最新文献_第3页

Virtual perspectives of sanguinarine on cancer prevention and treatment through molecular dynamic study. 通过分子动力学研究，虚拟透视番荔枝碱对癌症预防和治疗的作用。

In silico pharmacology Pub Date : 2025-02-25 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00315-7

Vikas Sharma, Arti Gupta, Anshul Singh, Shivani Tyagi, Hrithika Panday, Saurabh Srivastava, Sathvik Belagodu Sridhar, Safia Obaidur Rab, Sandeep Kumar Shukla

{"title":"Virtual perspectives of sanguinarine on cancer prevention and treatment through molecular dynamic study.","authors":"Vikas Sharma, Arti Gupta, Anshul Singh, Shivani Tyagi, Hrithika Panday, Saurabh Srivastava, Sathvik Belagodu Sridhar, Safia Obaidur Rab, Sandeep Kumar Shukla","doi":"10.1007/s40203-025-00315-7","DOIUrl":"10.1007/s40203-025-00315-7","url":null,"abstract":"Cancer prevention involves resisting cancer development at initial stages, retarding angiogenesis and initiating cancer cell apoptosis. Through the use of virtual screening, binding free energy calculations, and molecular dynamics simulations, we were able to identify compounds with potential anticancer activity.\"During the virtual screening process, compounds with promising drug-like properties were chosen using the Lipinski rule of five, and their binding affinities were evaluated by docking studies. In-silico activity of six different phytochemicals against established cancer specific proteins (NF-kB, p53, VEGF, BAX/BCl-2, TNF-alpha) were performed out of which p53, VEGF, BCl-2 has shown significant results. Sanguinarine has shown good docking score of -9.0 with VEGF and - 8.8 with Bcl-2 receptor and has been selected for molecular dynamics simulation. The results of Molecular Dynamics Simulations (MD) studies showed that RMSD and RMSF values of sanguinarine within an acceptable global minima (3-5.5 Å) for p53, VEGF, BAX/BCl-2. The computational models employed in this study produced important insights into the molecular mechanisms via which Sanguinarine prevents cancer by acting against p53, VEGF, and BCl-2 and by blocking the angiogenic, apoptotic, and proliferative pathways involved in the formation of cancer. The results suggest that the pharmacological activity of the selected phytomolecule (sanguinarine) is a promising avenue for cancer prevention.Graphical abstract: ","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular modeling of the interactions of compounds of Irvinga wombulu against dihydrofolate reductase-thymidylate synthase in Plasmodium falciparum towards development of anti-malarial drug.

In silico pharmacology Pub Date : 2025-02-19 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00317-5

Amarachi Chike-Ekwughe, Hassan Taiye Abdulameed, Grace I Adebayo-Gege, Abubakar Usman, Emmanuel Joy Omoyungbo, Adeola Adefoluke Ala, Abayomi Emmanuel Adegboyega, Titilayo Omolara Johnson

{"title":"Molecular modeling of the interactions of compounds of Irvinga wombulu against dihydrofolate reductase-thymidylate synthase in Plasmodium falciparum towards development of anti-malarial drug.","authors":"Amarachi Chike-Ekwughe, Hassan Taiye Abdulameed, Grace I Adebayo-Gege, Abubakar Usman, Emmanuel Joy Omoyungbo, Adeola Adefoluke Ala, Abayomi Emmanuel Adegboyega, Titilayo Omolara Johnson","doi":"10.1007/s40203-025-00317-5","DOIUrl":"10.1007/s40203-025-00317-5","url":null,"abstract":"Malaria is a significant global health burden that affects the majority of people in the world. Nigeria still accounts for the highest percentage of the worldwide malaria burden, with 27% of estimated malaria cases and 31% of estimated deaths due to malaria in 2022. While antimalarial effects have been attributed to some active compounds from medicinal plants, no study has been conducted on Irvingia wombulu (IW). Therefore, this study aimed to evaluate the in silico antimalarial activity of some active compounds identified after gas chromatography/mass spectrometry (GC/MS) studies on Irvingia wombolu. The compounds were docked against the anti-malaria target Dihydrofolate Reductase-Thymidylate Synthase (DHFR-TS) of Plasmodium falciparum with PDB ID 3QGT and their pharmacokinetic properties were also predicted. This was followed by a molecular dynamics (MD) simulation of the protein in complex with the most promising IW compound. The GC-MS result revealed 44 phytoconstituents from IW. The Docking analysis revealed the following best binding energies (kcal/mol): alpha-tocopherol-beta-D-mannoside (-11.289), gamma-tocopherol (- 7.308), and linolenic acid (- 6.822). MD Simulation showed that the selected compound exhibited a stable conformation in the active site of the flexible protein. Pharmacokinetics analysis suggested that the compounds will be orally bio-available when administered. Therefore, these results indicate that these compounds can be considered for experimental validation and further development into antimalarial drugs.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

De novo in silico screening of natural products for antidiabetic drug discovery: ADMET profiling, molecular docking, and molecular dynamics simulations.

In silico pharmacology Pub Date : 2025-02-17 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00320-w

Sulyman Olalekan Ibrahim, Yusuf Oloruntoyin Ayipo, Halimat Yusuf Lukman, Fatimah Aluko Abubakar, Asiat Na'Allah, Rashidat Arije Katibi-Abdullahi, Marili Funmilayo Zubair, Olubunmi Atolani

{"title":"De novo in silico screening of natural products for antidiabetic drug discovery: ADMET profiling, molecular docking, and molecular dynamics simulations.","authors":"Sulyman Olalekan Ibrahim, Yusuf Oloruntoyin Ayipo, Halimat Yusuf Lukman, Fatimah Aluko Abubakar, Asiat Na'Allah, Rashidat Arije Katibi-Abdullahi, Marili Funmilayo Zubair, Olubunmi Atolani","doi":"10.1007/s40203-025-00320-w","DOIUrl":"10.1007/s40203-025-00320-w","url":null,"abstract":"Epigenetic dysfunction which has implicated disease conditions such as diabetes highlights the urgency for the discovery of novel therapeutic alternatives. The rising global incidences of diabetes and the limitations of existing treatments further exacerbate the quest for novel antidiabetic agents' discovery. This study leverages computational approaches to screen selected bioactive natural product phytoconstituents for their potential anti-diabetic properties. Utilizing pharmaceutical profiling, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions, molecular docking, and molecular dynamics (MD) simulations, the drug-likeness and binding affinity of these natural compounds against human pancreatic amylase was investigated. Out of the total 24,316 ZINC compounds screened for their binding scores with amylase, ZINC85593620, ZINC85593668, and ZINC85490447 came top. The compounds had higher binding scores than the standards (acarbose and ranirestat) with ZINC85593620 having the highest docking score of - 12.162 kcal/mol and interacted with key amino acid residues such as TRP 59, ILE 148, and ASP 197. Further validation through MD simulations reveals that all the compounds showed minimal fluctuations relative to the standards indicating strong and stable binding interactions suggesting potential effective inhibition of the enzyme. ZINC85593620 and ZINC85593668 showed promising distribution and availability characteristics for amylase inhibition. Overall, the compounds displayed potential amylase inhibition which underscores their use as promising natural products in developing new antidiabetic drugs. Further experimental validations are recommended to offer a potential solution to the pressing need for safer and more effective antidiabetic therapies.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Afobazole: a potential drug candidate which can inhibit SARS CoV-2 and mimicry of the human respiratory pacemaker protein.

In silico pharmacology Pub Date : 2025-02-17 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00316-6

Govinda Rao Dabburu, Anjali Garg, Neelja Singhal, Manish Kumar

{"title":"Afobazole: a potential drug candidate which can inhibit SARS CoV-2 and mimicry of the human respiratory pacemaker protein.","authors":"Govinda Rao Dabburu, Anjali Garg, Neelja Singhal, Manish Kumar","doi":"10.1007/s40203-025-00316-6","DOIUrl":"10.1007/s40203-025-00316-6","url":null,"abstract":"In COVID-19 patients, respiratory failure was reported due to damage to the respiratory centers of the brainstem. Molecular mimicry of three brainstem pre-Botzinger complex proteins (DAB1, AIFM and SURF1) was regarded as the underlying reason for respiratory failure and the autoimmune neurological sequelae. Of the three brainstem proteins mimicked by SARS CoV-2, corresponding sequences to two of the mimicry peptides were located in the N-protein of SARS CoV-2. N-protein is important for viral RNA synthesis and genome packaging. Here, we have used molecular modeling, docking and MD simulations to discern potential drugs which can inhibit molecular mimicry of DAB1 by SARS CoV-2 and also eliminate it by interfering in genome packaging. The binding site (drug target) for molecular docking was defined as the amino acid sequence extending from position 168-185 of the N-protein which was a SLiM region and also included the mimicry hexapeptide. Molecular docking after MD simulations was used to discern probable inhibitors of the drug-target from FDA-approved neurological drugs in the Broad Institute's Drug Repurposing Hub. Our results revealed that an anti-anxiety drug afobazole qualified the ADMET parameters, formed a stable complex with the drug-target and exhibited the highest binding energy (-88.21 kJ/mol). This suggests that afobazole can be repurposed against SARS CoV-2 for disrupting molecular mimicry of human DAB1 protein and also eliminate the etiopathological agent by interfering in viral genome packaging.Graphical abstract: Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00316-6.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repurposing doxycycline for the inhibition of monkeypox virus DNA polymerase: a comprehensive computational study.

In silico pharmacology Pub Date : 2025-02-13 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00307-7

Muhammad Abrar Yousaf, Maurice Michel, Abeedha Tu-Allah Khan, Misbah Noreen, Saddia Bano

{"title":"Repurposing doxycycline for the inhibition of monkeypox virus DNA polymerase: a comprehensive computational study.","authors":"Muhammad Abrar Yousaf, Maurice Michel, Abeedha Tu-Allah Khan, Misbah Noreen, Saddia Bano","doi":"10.1007/s40203-025-00307-7","DOIUrl":"10.1007/s40203-025-00307-7","url":null,"abstract":"The global spread of monkeypox, caused by the double-stranded DNA monkeypox virus (MPXV), has underscored the urgent need for effective antiviral treatments. In this study, we aim to identify a potent inhibitor for MPXV DNA polymerase (DNAP), a critical enzyme in the virus replication process. Using a computational drug repurposing approach, we performed a virtual screening of 1615 FDA-approved drugs based on drug-likeness and molecular docking against DNAP. Among these, 1430 compounds met Lipinski's rule of five for drug-likeness, with Doxycycline emerging as the most promising competitive inhibitor, binding strongly to the DNAP active site with a binding affinity of - 9.3 kcal/mol. This interaction involved significant hydrogen bonds, electrostatic interactions, and hydrophobic contacts, with Doxycycline demonstrating a stronger affinity than established antivirals for smallpox, including Cidofovir, Brincidofovir, and Tecovirimat. Stability and flexibility analyses through a 200 ns molecular dynamics simulation and normal mode analysis confirmed the robustness of Doxycycline binding to DNAP. Overall, our results suggest Doxycycline as a promising candidate for monkeypox treatment, though additional experimental and clinical studies are needed to confirm its therapeutic potential and clinical utility.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00307-7.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tinospora cordifolia bioactive compounds as a novel sterol 14a-demethylase (CYP51) inhibitor: an in silico study.

In silico pharmacology Pub Date : 2025-02-13 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00312-w

Kolawole T Mesileya, Precious C Onyeka, Iyidola M Adaramola, Quareebat O Igbalaye, Damilola S Bodun, Wisdom K Alao, Salim Y Jibril, Mustapha S Mohammed, Adedayo S Bowaje, Adebisi M Adeleye, Olaposi I Omotuyi

{"title":"Tinospora cordifolia bioactive compounds as a novel sterol 14a-demethylase (CYP51) inhibitor: an in silico study.","authors":"Kolawole T Mesileya, Precious C Onyeka, Iyidola M Adaramola, Quareebat O Igbalaye, Damilola S Bodun, Wisdom K Alao, Salim Y Jibril, Mustapha S Mohammed, Adedayo S Bowaje, Adebisi M Adeleye, Olaposi I Omotuyi","doi":"10.1007/s40203-025-00312-w","DOIUrl":"10.1007/s40203-025-00312-w","url":null,"abstract":"Trypanosoma cruzi, the causative agent of Chagas disease, poses a life-threatening risk in both endemic and non-endemic regions. The parasite's survival depends on the production of sterols via the 14-α-demethylase (CYP51) metabolic pathway. Current treatments for Chagas disease are often associated with undesirable side effects and drug resistance. This study aimed to identify potential inhibitors of CYP51 using bioactive compounds derived from Tinospora cordifolia. A library of 122 compounds from T. cordifolia was screened against CYP51 using the Glide docking model in the Maestro-Schrodinger suite (2022). The top four leads were evaluated through e-pharmacophore modeling, pharmacokinetics (ADMET) analysis and molecular mechanics generalized Born surface area (MM-GBSA) calculations. The top four compounds exhibited superior binding affinity to CYP51 compared to the standard drug, benznidazole, with docking scores ranging from - 11.397 kcal/mol to - 9.539 kcal/mol. ADMET predictions suggested low cytotoxicity for these compounds. Among the leads, epicatechin and n-trans-caffeoyl tyramine showed the greatest stability, reduced flexibility, and compact conformations, making them promising candidates for further investigation. This study identifies potential inhibitors from T. cordifolia with high binding affinity and structural compatibility with CYP51. While these results are encouraging, further in vivo and in vitro studies are necessary to validate their efficacy as anti-Chagas agents.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00312-w.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In-silico evaluation of diffractaic acid as novel anti-diabetic inhibitor against dipeptidyl peptidase IV enzyme.

In silico pharmacology Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00321-9

Miah Roney, Abdul Rashid Issahaku, Amit Dubey, Aisha Tufail, S M Istiaque Hamim, Anke Wilhelm, Mohd Fadhlizil Fasihi Mohd Aluwi

{"title":"In-silico evaluation of diffractaic acid as novel anti-diabetic inhibitor against dipeptidyl peptidase IV enzyme.","authors":"Miah Roney, Abdul Rashid Issahaku, Amit Dubey, Aisha Tufail, S M Istiaque Hamim, Anke Wilhelm, Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1007/s40203-025-00321-9","DOIUrl":"10.1007/s40203-025-00321-9","url":null,"abstract":"Diabetes mellitus (DM) is one of the most common long-term metabolic illnesses with detrimental implications on health and 90-95% of DM cases worldwide are caused by type 2 diabetes (T2DM). The side effects of the existing medicines include vomiting, diarrhea, and serious damage to the kidneys, blood vessels, and nerves. Therefore, finding anti-diabetic medications without side effects is crucial. The main goal of this work is to find anti-diabetic inhibitors using in-silico evaluation techniques such as molecular docking, molecular dynamic simulation, principal component analysis, and drug probability analysis. The DPP-IV is one of numerous molecular targets implicated in the pathogenesis of DM and Diffractaic acid (DF) was docked into the active site of this enzyme to assess the inhibitory effect of DF. In addition, MD simulation and PCA were used to assess the stability of docked complex. Furthermore, the DF was then subjected to drug probability investigations. The binding affinity of the DF was - 40.2476 kcal/mol, which was comparable to the reference compound (- 43.0908 kcal/mol). Furthermore, the compound was in a stable structure, as demonstrated by MD simulation and PCA analysis. Based on drug probability tests, DF also demonstrated druggable qualities. The results of this investigation suggest that DF may function as a possible inhibitor against DM; nevertheless, more in vitro and in vivo investigations are required to validate the activity and other properties.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00321-9.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular detection of mecA gene from methicillin-resistant Staphylococcus aureus isolated from clinical and environmental samples and its potential inhibition by phytochemicals using in vitro and in silico approach.

In silico pharmacology Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-024-00297-y

Mohammed M Mohammed, Mustafa Alhaji Isa, Mustapha B Abubakar, Abubakar Sadiq Baba Dikwa, Abidemi Paul Kappo

{"title":"Molecular detection of mecA gene from methicillin-resistant Staphylococcus aureus isolated from clinical and environmental samples and its potential inhibition by phytochemicals using in vitro and in silico approach.","authors":"Mohammed M Mohammed, Mustafa Alhaji Isa, Mustapha B Abubakar, Abubakar Sadiq Baba Dikwa, Abidemi Paul Kappo","doi":"10.1007/s40203-024-00297-y","DOIUrl":"10.1007/s40203-024-00297-y","url":null,"abstract":"The increasing prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) has posed significant challenges in clinical and environmental settings. MRSA's resistance is attributed to the mecA gene, which encodes the penicillin-binding protein 2a (PBP2a), conferring resistance to β-lactam antibiotics. This study aimed to molecularly detect the mecA gene in MRSA isolates from clinical and environmental samples and identify potential inhibitors of PBP2a using in vitro and in silico approaches. A total of 180 samples were collected, isolating 64 Staphylococcus aureus strains, of which 10 (37%) were confirmed as MRSA. Molecular detection confirmed the presence of the mecA gene in these isolates. Phytochemical analysis of Acacia nilotica and Mangifera indica extracts revealed bioactive compounds with antimicrobial properties. In vitro antimicrobial testing showed the plant extracts demonstrated significant inhibitory effects against MRSA, with minimum inhibitory concentrations (MIC) ranging from 0 to 6.20 mg/mL. Molecular docking and molecular dynamics simulation analyses identified three compounds (CID_628694, CID_546930, and CID_620007) with strong binding affinities and stable interactions with PBP2a, suggesting their potential as novel inhibitors. These findings highlight the therapeutic potential of phytochemicals in combating MRSA and provide a basis for future experimental validations.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prediction of SafD adhesin strong binding peptides for pilus proteins assembly suppression in the prevention of Salmonella-induced biofilm formation using virtual mutagenesis studies.

In silico pharmacology Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00313-9

Priyanka Samanta, Sourav Ghorai

{"title":"Prediction of SafD adhesin strong binding peptides for pilus proteins assembly suppression in the prevention of Salmonella-induced biofilm formation using virtual mutagenesis studies.","authors":"Priyanka Samanta, Sourav Ghorai","doi":"10.1007/s40203-025-00313-9","DOIUrl":"10.1007/s40203-025-00313-9","url":null,"abstract":"Clinical isolates of Salmonella enterica contain Saf pili that establish initial bacterial attachment with the human epithelium to form biofilms which are a common cause of several abdominal complications. Due to the rise in antibiotic-resistant strains of bacteria, an alternate strategy of inhibiting the initial bacterial contact with the epithelial layers is well-studied. Saf pili undergo a chaperone-usher pathway assembly mechanism to generate its host-recognizing functional form, SafDAA. Preventing the biogenesis of the pili by targeting the SafD and SafA proteins polymerization will prevent host recognition. In this study, virtual mutagenesis studies using the recently reported X-ray crystal structure of an N-terminal peptide co-crystallized with SafD led to the design of peptides that exhibit enhanced binding with SafD compared to its native peptide. Virtual alanine mutagenesis and protein-peptide interaction studies identified several hotspot residues. Molecular dynamics simulations and binding free energy calculations identified key pairwise interactions between the designed peptides and SafD. In addition, a library of 110 peptides that are predicted to bind strongly with SafD is prepared which can serve as an excellent resource for the discovery of novel SafD-binding peptides. This work provided new insights into the design of novel anti-virulence therapies targeting Salmonella enterica.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00313-9.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"25"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computer aided design of inhibitor molecules against Vpr protein from different HIV-1 subtypes.

In silico pharmacology Pub Date : 2025-02-08 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00318-4

Joyeeta Datta, Satyabrata Majumder, Kalyan Giri

{"title":"Computer aided design of inhibitor molecules against Vpr protein from different HIV-1 subtypes.","authors":"Joyeeta Datta, Satyabrata Majumder, Kalyan Giri","doi":"10.1007/s40203-025-00318-4","DOIUrl":"10.1007/s40203-025-00318-4","url":null,"abstract":"HIV-1 is a retrovirus that affects the human immune system and consequently leads to the development of AIDS. The high mutation rate in HIV-1 produces different subtypes which underscores the development of new therapeutics against it. This study aims to develop a novel small molecule that can be used as a potential inhibitor against the Vpr protein of all the subtypes of HIV-1. The druggable pockets of the Vpr protein of each subtype were identified and the conformational stability of these pockets was studied. The structure-based Drug Design method was used to design small molecules against the high-scoring pocket from each subtype individually using AutoGrow4 software. Molecules with strong binding affinity were selected from each subtype individually and binding affinity was checked for all the subtypes. Considering druggability and ADMET properties, we have identified two novel molecules that act as potential Vpr protein inhibitors. Both the molecules were shown to form stable complexes with the Vpr proteins of all the subtypes. The biological activity of both molecules was examined using DFT calculation. This study may provide some insight into developing of new therapies in HIV-1 treatment by interrupting protein-protein interaction.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00318-4.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0