Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Investigation of the molecular basis of halogenated Schiff base derivative by combined crystallographic and computational studies.","authors":"M Siddesh, R Sharanya, L Spoorthy, Dhruva Bhat, A H Udaya Kumar, Mahesha, M K Hema, N K Lokanath","doi":"10.1080/07391102.2023.2301512","DOIUrl":"10.1080/07391102.2023.2301512","url":null,"abstract":"<p><p>Halogenated Schiff base derivatives are gaining more popularity in supramolecular chemistry due to the synergistic effect of hydrogen and halogen-based noncovalent interactions, which helps to design novel therapeutic materials. In this work, we have examined the nature of molecular interactions to investigate the structure-functional relationship of a halogen-based derivative. The FTIR, HRMS and NMR spectroscopic techniques confirmed the formation of the desired novel Schiff base compound. Further, crystal structure studies showed an infinite 1D supramolecular chain formed by type-I halogen…halogen interaction. The Hirshfeld surface and enrichment ratio analyses were performed to visualize and assess the role of diverse interactions involved in crystal packing. The QTAIM, NCI, LOL and ELF studies were conducted extensively to comprehend the strength of interaction constructed based on electron density distribution. The global and local reactive indices were determined using DFT studies to analyze the molecular properties of the compound. Antibacterial activity against MRSA bacteria was performed and showed a good zone of inhibition. The docking analysis was performed for 1mwt protein and validated. The <i>in silico</i> molecular docking studies of the halogenated Schiff base structure with the penicillin-binding protein showed a good docking affinity of -7.5 kcal/mol and supported by <i>in vitro</i> studies. The ligand binding stability within the protein's active site was further demonstrated by molecular dynamics (MD) simulation studies for the Schiff base molecule.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2479-2490"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377689","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}

{"title":"A computational study on structural and functional consequences of nsSNPs in human dopa decarboxylase.","authors":"S Birendra Kumar, Aishwarya Girish, Samruddhi Sutar, Suheeth Amberi Premanand, Vrinda Garg, Arvind Kumar Yadav, Rohit Shukla, T P Krishna Murthy, Tiratha Raj Singh","doi":"10.1080/07391102.2023.2301517","DOIUrl":"10.1080/07391102.2023.2301517","url":null,"abstract":"<p><p>The Dopa Decarboxylase (DDC) gene plays an important role in the synthesis of biogenic amines such as dopamine, serotonin, and histamine. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the DDC gene have been linked with various neurodegenerative disorders. In this study, a comprehensive <i>in silico</i> analysis of nsSNPs in the DDC gene was conducted to assess their potential functional consequences and associations with disease outcomes. Using publicly available databases, a complete list of nsSNPs in the DDC gene was obtained. 29 computational tools and algorithms were used to characterise the effects of these nsSNPs on protein structure, function, and stability. In addition, the population-based association studies were performed to investigate possible associations between specific nsSNPs and arthritis. Our research identified four novel DDC gene nsSNPs that have a major impact on the structure and function of proteins. Through molecular dynamics simulations (MDS), we observed changes in the stability of the DDC protein induced by specific nsSNPs. Furthermore, population-based association studies have revealed potential associations between certain DDC nsSNPs and various neurological disorders, including Parkinson's disease and dementia. The <i>in silico</i> approach used in this study offers insightful information about the functional effects of nsSNPs in the DDC gene. These discoveries provide insight into the cellular processes that underlie cognitive disorders. Furthermore, the detection of disease-associated nsSNPs in the DDC gene may facilitate the development of tailored and targeted therapy approaches.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2503-2517"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403025","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}

{"title":"Enhancing solubility and stability of piperine using β-cyclodextrin derivatives: computational and experimental investigations.","authors":"Saba Ali, Phattharapawn Saokaew, Aamir Aman, Duangjai Todsaporn, Kamonpan Sanachai, Kuakarun Krusong, Supot Hannongbua, Peter Wolschann, Panupong Mahalapbutr, Thanyada Rungrotmongkol","doi":"10.1080/07391102.2024.2305696","DOIUrl":"10.1080/07391102.2024.2305696","url":null,"abstract":"<p><p>Piperine (PP), a natural alkaloid found in black pepper, possesses significant bioactivities. However, its use in pharmaceutical applications is hindered by low water solubility and susceptibility to UV light degradation. To overcome these challenges, we investigated the potential of β-cyclodextrin (βCD) and its derivatives with dimethyl (DMβCD), hydroxy-propyl (HPβCD) and sulfobutyl-ether (SBEβCD) substitutions to enhance the solubility and stability of PP. This study employed computational and experimental approaches to examine the complexation between PP and βCDs. The results revealed the formation of two types of inclusion complexes: the P-form and M-form involving the insertion of piperidine moiety and the methylene-di-oxy-phenyl moiety, respectively. These complexes primarily rely on van der Waals interactions. Among the three derivatives, the PP/SBEβCD complex exhibited the highest stability followed by HPβCD, as attributed to maximum atom contacts and minimal solvent accessibility. Solubility studies confirmed the formation of inclusion complexes in a 1:1 ratio. Notably, the stability constant of the inclusion complex was approximately two-fold higher with SBEβCD and HPβCD compared to βCD. The DSC thermograms provided confirmation of the formation of the inclusion complex between the host and guest. These findings highlight the potential of βCD derivatives to effectively encapsulate PP, improving its solubility and presenting new opportunities for its pharmaceutical applications.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2596-2609"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521098","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}

{"title":"<i>In silico</i> approach reveals <i>N</i>-(5-phenoxythiophen-2-yl)-2-(arylthio)acetamides as promising selective SIRT2 inhibitors: the case of structural optimization of virtual screening-derived hits.","authors":"Mahmut Gozelle, Filiz Bakar-Ates, Alberto Massarotti, Erva Ozkan, Habibe Beyza Gunindi, Yesim Ozkan, Gokcen Eren","doi":"10.1080/07391102.2023.2293252","DOIUrl":"10.1080/07391102.2023.2293252","url":null,"abstract":"<p><p>Epigenetic modifications play an essential role in tumor suppression and promotion. Among the diverse range of epigenetic regulators, SIRT2, a member of NAD⁺-dependent protein deacetylates, has emerged as a crucial regulator of cellular processes, including cell cycle progression, DNA repair, and metabolism, impacting tumor growth and survival. In the present work, a series of <i>N</i>-(5-phenoxythiophen-2-yl)-2-(arylthio)acetamide derivatives were identified following a structural optimization of previously reported virtual screening hits, accompanied by enhanced SIRT2 inhibitory potency. Among the compounds, <b>ST44</b> and <b>ST45</b> selectively inhibited SIRT2 with IC₅₀ values of 6.50 and 7.24 μM, respectively. The predicted binding modes of the two compounds revealed the success of the optimization run. Moreover, <b>ST44</b> displayed antiproliferative effects on the MCF-7 human breast cancer cell line. Further, the contribution of SIRT2 inhibition in this effect of <b>ST44</b> was supported by western blotting, affording an increased α-tubulin acetylation. Furthermore, molecular dynamics (MD) simulations and binding free energy calculations using molecular mechanics/generalized born surface area (MM-GBSA) method evaluated the accuracy of predicted binding poses and ligand affinities. The results revealed that <b>ST44</b> exhibited a remarkable level of stability, with minimal deviations from its initial docking conformation. These findings represented a significant improvement over the virtual screening hits and may contribute substantially to our knowledge for further selective SIRT2 drug discovery.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1756-1767"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803267","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}

{"title":"Identification of promising small-molecule inhibitors targeting STK17B for cancer therapeutics: molecular docking and molecular dynamics investigations.","authors":"Modinat Wuraola Akinboade, Abel Ujaigbe Egbemhenghe, Teslim Oluwaseyi Abdulkareem, Ismail Abiola Ibrahim, Bamidele Samson Omotara, Olajide Enoch Aderemi, Winner Amaka Egejuru, Chinedum Favour Ajala, Ihunanya Meejay Kanu, Oluwatosin Oluwafunmilola Oluwafemi, Christiana Oluwaseun Aderemi, Christopher Ddamulira, Akinwumi Raphael Afuape, Adedayo Toluwanimi Adekola, Toluwalase Ojeyemi, Osasenaga Israel Otuomagie","doi":"10.1080/07391102.2023.2296605","DOIUrl":"10.1080/07391102.2023.2296605","url":null,"abstract":"<p><p>Cancer is a complex disease characterized by the uncontrolled growth of abnormal cells, leading to the formation of tumours. STK17B, a member of the DAPK family, has been implicated in various cancers and is considered a potential therapeutic target. However, no drug in the market has been approved for the treatment of STK17 B-associated cancer disease. This research aimed to identify direct inhibitors of STK17B using computational techniques. Ligand-based virtual screening and molecular docking were performed, resulting in the selection of three lead compounds (CID_135698391, CID_135453100, CID_136599608) with superior binding affinities compared to the reference compound dovitinib. While molecular docking simulation revealed specific interactions between the lead compounds and key amino acid residues at the binding pocket of STK17B, molecular dynamics simulations demonstrated that CID_135453100 and CID_136599608 exhibit stable conformations and comparable flexibility to dovitinib. However, CID_135698391 did not perform well using this metric as it displayed poor stability. Overall, small-molecule compounds CID_135453100 and CID_136599608 showed promising binding interactions and stability, suggesting their potential as direct inhibitors of STK17B. These findings could contribute to the exploration of novel therapeutic options targeting STK17B in cancer treatment.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2389-2396"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040041","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}

{"title":"Bioprospecting of Meliaceae family phytomolecules for the treatment of monkeypox virus infection: a QSAR modeling and MD simulation approach.","authors":"Ali A Rabaan, Muhammad A Halwani, Ahmad A Alshehri, Maha F Al-Subaie, Zainab H Almansour, Bashayer M AlShehail, Nouf Alotaibi, Faryal Khamis, Nawal A Al Kaabi, Ghaneema Alsomali, Ali S Alqahtani, Mohammed Alissa","doi":"10.1080/07391102.2023.2294180","DOIUrl":"10.1080/07391102.2023.2294180","url":null,"abstract":"<p><p>Recent monkeypox virus (MPXV) infections show the risk of MPXV transmission that persists today and the significance of surveillance and quick response methods to stop the virus's spread. Currently, the monkeypox virus infection is not specifically treated. In this study, QSAR models were designed using known inhibitors of cysteine proteinase from the vaccinia virus, where the Random Forest model and Ridge model had showed the best correlation between predicted and observed EC₅₀. These models were used to screen <i>Maliaceae</i> family phytochemicals against MPXV cysteine proteinase. The compound, IMPHY010637 was detected in top 5 from both the QSAR screening models and showed best docked score (-8.6 kcal/mol) and thus selected for further investigation. Further, the IMPHY010637 showed interaction with the catalytic residue His²⁴¹ of the protein as reported in earlier studies. The ADMET analysis of the compound showed the acceptable drug-like properties of IMPHY010637. However, these properties could be improved after experimental validation of protein-ligand binding. Both docked complex and poses created in 100 ns MD simulation of the protein-ligand complex showed the presence of multiple hydrogen bonds. RMSD and conformation analysis showed stable binding of IMPHY010637 with the cysteine proteinase of MPXV at its active site. Compared to the known inhibitor, IMPHY010637 showed better binding with the protein as observed by the PCA and MM/GBSA analysis. This study concluded IMPHY010637 as a potential inhibitor for the cysteine proteinase of MPXV using computational methods that could be tested in <i>in-vitro</i> experiments.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2277-2299"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087028","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}

{"title":"Acetyl barlerin from <i>Barleria trispinosa</i> induces chemopreventive NQO1 and attenuates LPS-induced inflammation: <i>in vitro</i> and molecular dynamic studies.","authors":"Hamza M Assiry, Ahmed R Hamed, Gamal A Mohamed, Sabrin R M Ibrahim, Abdulrahman E Koshak, Azizah M Malebari, Sana A Fadil, Hossam M Abdallah","doi":"10.1080/07391102.2023.2293272","DOIUrl":"10.1080/07391102.2023.2293272","url":null,"abstract":"<p><p>Extraction and fractionation of <i>Barleria trispinosa</i> growing in Saudi Arabia yielded four iridoid compounds identified by spectroscopic techniques as acetylbarlerin (<b>1</b>), barlerin (<b>2</b>), shanzhiside methyl ester (<b>3</b>) and 6-⍺-L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester (<b>4</b>). Preliminary experiments confirmed that compound <b>1</b> acts as an inducer of chemopreventive NAD(P)H:Quinone oxidoreductase 1 (NQO1) enzymatic activity in a murine hepatoma (Hepa1c1c7) chemoprevention model. It also demonstrated the ability to inhibit the lipopolysaccharides (LPS)-induced nitric oxide (NO) production in the RAW264.7 macrophage model. Western blotting revealed the ability of compound <b>1</b> to up-regulate the protein expression of the NQO1 marker. Furthermore, compound <b>1</b> elicited NO suppression in RAW264.7 macrophages by inhibiting iNOS protein expression. Molecular docking and molecular simulation studies of <b>1</b> supported its experimental results as an inhibitor of the nuclear factor erythroid 2-Kelch-like ECH-associated protein 1 (Nrf2-KEAP1) complex, resulting in Nrf2-mediated induction of chemopreventive NQO1.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2002-2013"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803593","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}

{"title":"New nicotinamide derivatives as potential anticancer agents targeting VEGFR-2: design, synthesis, <i>in vitro</i>, and <i>in silico</i> studies.","authors":"Reda G Yousef, Ibrahim H Eissa, Hazem Elkady, Wagdy M Eldehna, Ahmed B M Mehany, Ahmed Nabeeh, Ibrahim M Ibrahim, Alaa Elwan, Mohamed Ayman El-Zahabi","doi":"10.1080/07391102.2023.2294170","DOIUrl":"10.1080/07391102.2023.2294170","url":null,"abstract":"<p><p>Herin, new nicotinamide candidates were designed and synthesized as VEGFR-2 inhibitors. <i>In vitro</i> antiproliferative activities were assessed against MCF-7, HepG-2 and HCT-116 cancer cell lines. The top cytotoxic members <b>15a</b>, <b>15b</b>, <b>16, 18a</b>, and <b>18b</b> were estimated against their selected target (VEGFR-2). Further mechanistic tests were studied for the most potent cytotoxic candidate <b>18a</b>, these studies revealed the ability of compound <b>18a</b> to hinder the progression of HCT-116 cells at S and Pre-G1phases besides boosting early and late apoptosis. Also compound <b>18a</b> was found to significantly decrease the levels immunomodulatory proteins TNF-α and IL-6 while showing a four-fold rise in an apoptotic marker caspase-3 when compared to control cells. The therapeutic index of the designed derivatives was evaluated by computational ADMET and toxicity calculations as well as their potentiality to occupy the VEGFR-2 active site was signposted by molecular docking assessments. Finally, molecular dynamic simulation studies of compound <b>18a</b>-VEGFR-2 complex indicated the high steadiness of compound <b>18a</b> in the VEGFR-2 active site. This study presents compound <b>18a</b> as a lead candidate that can be optimized to get a strong VEGFR-2 inhibitor.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2120-2137"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803928","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}

{"title":"Whole proteome analysis of MDR <i>Klebsiella pneumoniae</i> to identify mRNA and multiple epitope based vaccine targets against emerging nosocomial and lungs associated infections.","authors":"Muhammad Naveed, Khizra Jabeen, Tariq Aziz, Muhammad Saad Mughual, Jawad Ul-Hassan, Mohsin Sheraz, Hafiz Muzzammel Rehman, Metab Alharbi, Thamer H Albekairi, Abdullah F Alasmari","doi":"10.1080/07391102.2023.2293266","DOIUrl":"10.1080/07391102.2023.2293266","url":null,"abstract":"<p><p><i>Klebsiella pneumonia</i> is a Gram negative facultative anaerobic bacterium involved in various community-acquired pneumonia, nosocomial and lungs associated infections. Frequent usage of several antibiotics and acquired resistance mechanisms has made this bacterium multi-drug resistance (MDR), complicating the treatment of patients. To avoid the spread of this bacterium, there is an urgent need to develop a vaccine based on immuno-informatics approaches that is more efficient than conventional method of vaccine prediction or development. Initially, the complete proteomic sequence of <i>K. pneumonia</i> was picked over for specific and prospective vaccine targets. From the annotation of the whole proteome, eight immunogenic proteins were selected, and these shortlisted proteins were interpreted for CTL, B-cells, and HTL epitopes prediction, to construct mRNA and multi-epitope vaccines. The Antigenicity, allergenicity and toxicity analysis validate the vaccine's design, and its molecular docking was done with immuno-receptor the TLR-3. The docking interaction showed a stronger binding affinity with a minimum energy of -1153.2 kcal/mol and established 23 hydrogen bonds, 3 salt bridges, 1 disulfide bond, and 340 non-binding contacts. Further validation was done using <i>In-silico</i> cloning which shows the highest CAI score of 0.98 with higher GC contents of 72.25% which represents a vaccine construct with a high value of expression in <i>E. coli.</i> Immune Simulation shows that the antibodies (IgM, IgG1, and IgG2) production exceeded 650,000 in 2 to 3 days but the response was completely neutralized in the 5^th day. In conclusion, the study provides the effective, safe and stable vaccine construct against <i>Klebsiella pneumonia,</i> which further needs <i>in vitro</i> and <i>in vivo</i> validations.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1915-1928"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032358","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}

{"title":"Structure-guided screening of protein-protein interaction for the identification of Myc-Max heterodimer complex modulators.","authors":"Shovonlal Bhowmick, Kunal Roy, Achintya Saha","doi":"10.1080/07391102.2023.2294174","DOIUrl":"10.1080/07391102.2023.2294174","url":null,"abstract":"<p><p>De-regulation of oncogenic myelocytomatosis (c-Myc or Myc) transcription factor is one of the most common molecular anomalies encountered in human cancers, and it is typically linked to many aggressive malignancies including breast, lung, cervix, colon glioblastomas, and other haematological organs. The Myc belongs to the basic helix-loop-helix zipper protein family (bHLH-ZIP), and its dimerization with another principal interactor protein partner Myc-associated factor X (Max) is essentially required for cellular transformation, cell growth and proliferation, and transcriptional activation. Intermolecular interactions have been evaluated between hetero-dimer Myc-Max protein, which identified protein-protein interaction (PPI) specific modulators using highly précised molecular docking study followed by long-range interaction stability analyzed through molecular dynamic (MD) simulation. Moreover, ADME profile analyses have been estimated for screened hit compounds. MM-GBSA-based binding free energy (ΔG) estimations have been performed for all screened hit compounds obtained from multi-step molecular docking-based virtual screening technique. According to the employed various rigorous multi-chemometric techniques, four identified inhibitors/modulators appear to have a considerable number of intermolecular contacts with hotspot residues in the hetero-dimer interface region of the Myc-Max PPI complex. However, identified hit compounds might need further structural optimization or extensive biophysical analyses for better understanding of the molecular mechanism for exhibiting the Myc-Max PPI interface binding stability.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2204-2222"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804090","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}