Journal of Biomolecular Structure & Dynamics最新文献_第9页

Nitrogen-containing heterocycles as important scaffold for selective and potent HDAC8 inhibition: a step towards effective, non-toxic and selective HDAC8 inhibitor discovery.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-24 DOI: 10.1080/07391102.2024.2442756

Samima Khatun, Rakibul Islam, Sk Abdul Amin, Arijit Bhattacharya, Devendra Kumar Dhaked, Tarun Jha, Shovanlal Gayen

{"title":"Nitrogen-containing heterocycles as important scaffold for selective and potent HDAC8 inhibition: a step towards effective, non-toxic and selective HDAC8 inhibitor discovery.","authors":"Samima Khatun, Rakibul Islam, Sk Abdul Amin, Arijit Bhattacharya, Devendra Kumar Dhaked, Tarun Jha, Shovanlal Gayen","doi":"10.1080/07391102.2024.2442756","DOIUrl":"https://doi.org/10.1080/07391102.2024.2442756","url":null,"abstract":"Selective inhibition of histone deacetylase 8 (HDAC8) has emerged as a promising approach for treating various diseases, including cancer. However, finding key structural features for HDAC8 inhibition and developing effective and selective HDAC8 inhibitors (HDAC8is) pose significant challenges. In the past few years, the development of various scaffolds for inhibiting HDAC8 has significantly risen and the quest continues. In such cases, N-heterocyclic derivatives (such as thiazine, indole/pyrrole, pyrazole, triazole, indole, etc.) can play a crucial role in the discovery of novel selective HDAC8 inhibitors. In this current work, Bayesian and SARpy QSAR models were established on a structurally diverse set of 188 selective HDAC8 inhibitors after an extensive literature search. QSAR modelling suggests N-heterocyclic rings as important structural fingerprints for selective as well as promising HDAC8 inhibition. Further, molecular docking and molecular dynamics (MD) simulation studies were carried out on selected compounds (4, 15, 36, 40, and 188) containing N-heterocyclic rings to emphasize the significance of these scaffolds in HDAC8 potency. In addition to this, toxicity studies were carried out using density functional theory (DFT) to determine the toxicity profile of investigated compounds which indicated that the compounds are non-toxic. The outcomes of this research will aid in the exploration of certain key directions for the selective HDAC8 inhibitor design that could speed up the search for anticancer drugs.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881261","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

Identification of a potential anti-viral drug targeting allosteric site of papain-like protease against rubella using a molecular modeling approach.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-23 DOI: 10.1080/07391102.2024.2443132

Vrinda Salvi, Purva Khodke, Pruthanka Patil, Bajarang Vasant Kumbhar

{"title":"Identification of a potential anti-viral drug targeting allosteric site of papain-like protease against rubella using a molecular modeling approach.","authors":"Vrinda Salvi, Purva Khodke, Pruthanka Patil, Bajarang Vasant Kumbhar","doi":"10.1080/07391102.2024.2443132","DOIUrl":"https://doi.org/10.1080/07391102.2024.2443132","url":null,"abstract":"Rubella virus (RUBV) is responsible for causing rashes, lymphadenopathy, and fever which are the hallmarks of an acute viral illness called Rubella. For RUBV replication, the non-structural polyprotein p200 must be cleaved by the rubella papain-like protease (RubPro) into the multifunctional proteins p150 and p90. Hence, RubPro is an attractive target for anti-viral drug discovery. Moreover, the binding of host Calmodulin 1 (CaM) to RubPro modulates the protease activity and infectivity of RUBV. However, the binding mode of CaM and RubPro remain uncertain. Therefore, our investigation not only delves into understanding the interaction between CaM and the RubPro but also aims to recognize the allosteric site for the development of antiviral protease inhibitors. In this study, we interestingly identified the allosteric site in close vicinity with the CaM binding domain of RubPro. Considering the allosteric site of RubPro, we employed a computational modelling approach to identify the potential antiviral compounds. Leveraging ChemDiv protease inhibitors database, we employed structure-based virtual screening, ADME, pass prediction, and docking studies, unveiling three potent compounds: C073-2897, C073-3328, and C073-3368. Moreover, molecular dynamics simulation analysis revealed that these compounds affect the RubPro structure and dynamics and may also influence the binding of CaM with RubPro. Notably, binding energy calculation showed that the compound C073-3328 exhibits higher binding affinity, while C073-3368 displays a lower binding affinity with RubPro. These compounds signify potential for managing RUBV infections and pioneering effective antiviral treatments. This computational study could pave the way for improved methods of managing or controlling rubella infections.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876748","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 structure-guided and fragment-based inhibitor design to combat bedaquiline resistant Mycobacterium tuberculosis: a molecular dynamics study.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-23 DOI: 10.1080/07391102.2024.2441426

Alankar Roy, Prantik Banerjee, Ishani Paul, Ritam Ghosh, Sujay Ray

{"title":"Integrating structure-guided and fragment-based inhibitor design to combat bedaquiline resistant Mycobacterium tuberculosis: a molecular dynamics study.","authors":"Alankar Roy, Prantik Banerjee, Ishani Paul, Ritam Ghosh, Sujay Ray","doi":"10.1080/07391102.2024.2441426","DOIUrl":"https://doi.org/10.1080/07391102.2024.2441426","url":null,"abstract":"The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F0 region of enzyme ATP synthase of Mycobacterium tuberculosis, thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties. For this purpose, we adopted techniques like molecular dynamics simulation, virtual screening, PCA, DCCM, binding affinity analysis to gauge structure-function relationship of the L136-ATPc complexes. L136 was found to induce a distinguishable conformational change in the bound ATPc which captivated the c9 rotor ring. L136 displays a binding free energy of -57.294, -59.027, -57.273, -58.726, -55.889 and -58.651 kcal/mol for ATPc_WT and the five respective mutants. The pIC50 value for the L136 ligand for the same proteins was unveiled to be 6.760, 7.285, 6.898, 7.222, 6.987 and 7.687. Moreover, L136 exhibited a strong ADMET profile. Furthermore, we discovered that the change in the hydrophobic platform in ATPc mutants hinders BDQ binding, which is overcome by L136, ensuring efficient binding and providing an assessment of L136's mechanism of ATPc inhibition. L136 provides a scope for in vivo test for future clinical drug trials.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-39"},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876786","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

In silico studies of triazole derivatives as inhibitors for estrogen receptor (ER) mutant L536S and anaplastic lymphoma kinase: DFT/tD-DFT, molecular docking, and MD simulations.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-23 DOI: 10.1080/07391102.2024.2434688

Raushan Anjum, Kalpna Jain, Kalawati Meena, Amita Dua

{"title":"In silico studies of triazole derivatives as inhibitors for estrogen receptor (ER) mutant L536S and anaplastic lymphoma kinase: DFT/tD-DFT, molecular docking, and MD simulations.","authors":"Raushan Anjum, Kalpna Jain, Kalawati Meena, Amita Dua","doi":"10.1080/07391102.2024.2434688","DOIUrl":"https://doi.org/10.1080/07391102.2024.2434688","url":null,"abstract":"From the most prevalent cancers, breast and lung cancers have a meager survival rate for both men and women. These two cancers are related to each other. Breast cancer can possibly spread to the lungs or the region between the lung and the chest wall. The organic heterocyclic compounds are expected to possess some anti-cancerous properties. Hence, this study is to investigate the molecular characteristics of the derivatives of alkyl-5-hydroxy-7-aryl-5-methyl-1,3-dioxo-2-phenyl hexahydropyrazolo[1,2a] (Asif, 2017; Hei et al., 1996; Kumar et al., 2013) triazole-6-carboxylate and the drugability of these compounds have also been examined against estrogen receptor (ER) mutant L536S, which causes ER-positive breast cancer, and anaplastic lymphoma kinase responsible for non-small cell lung cancer (NSCLC). DFT and TDDFT have been used to study all the derivatives with B3LYP/6-311++G(d, p) basis set. Substituent effects via 1H NMR,13C NMR, IR, UV and HOMO-LUMO energy gaps of -CH3, -F, -Cl, -Br, -I, -NO2, and -SO3H groups at the para positions of 7-aryl substituent present in triazole compound have been studied. The global reactivity of these compounds is also being discussed in terms of band gap (EHOMO-ELUMO). The NTO analysis monitors and characterizes the direction and nature of charge transfer. The drug-likeness using Lipinski's Rule of Five, followed by molecular docking of the compounds with the target proteins have also been studied. Molecular dynamics simulations and free energy calculations were conducted for all protein-ligand complexes to predict potential inhibitors targeting the proteins.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-23"},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881256","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

In silico identification of Nipah virus protein inhibitors from secondary metabolites of medicinal plants using a high-throughput virtual screening approach.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-23 DOI: 10.1080/07391102.2024.2443131

John Christian C de Guzman, Albert Neil G Dulay, Fredmoore L Orosco

{"title":"In silico identification of Nipah virus protein inhibitors from secondary metabolites of medicinal plants using a high-throughput virtual screening approach.","authors":"John Christian C de Guzman, Albert Neil G Dulay, Fredmoore L Orosco","doi":"10.1080/07391102.2024.2443131","DOIUrl":"https://doi.org/10.1080/07391102.2024.2443131","url":null,"abstract":"The Nipah virus (NiV), a highly pathogenic zoonotic virus of the Paramyxoviridae family, poses significant threats with its alarming mortality rates and pandemic potential. Despite historical cases, effective therapeutics remain elusive, prompting urgent exploration of potential antivirals. In this study, a structure-based virtual screening approach was employed to evaluate 690 metabolites sourced from ten medicinal plants (Allium sativum, Andrographis paniculata, Cocos nucifera, Euphorbia hirta, Euphorbia neriifolia, Moringa oreifera, Ocimum basilicum, Piper nigrum, Vitex negundo, and Zingiber officinale) for their antiviral activity against Nipah virus proteins. Through targeted and blind docking experiments, forty-three (43) compounds were found to exhibit high binding affinities (≤ -8 Kcal mol-1) and validated site-specificity. Subsequent analysis of the ADMET properties of these compounds, along with off-target docking to swine receptors, six (6) compounds with profiles akin to approved drugs and minimal off-target binding were identified. Stability screening via 100 ns and 300 ns molecular dynamics simulations identified two (2) of the six compounds that demonstrated sustained dynamic stability over an extended duration, coupled with favorable binding energies from MM-(GB/PB)SA calculations and biologically significant binding modes and residue interactions. Betulinic acid and CID 118716357 exhibited significant potential as inhibitors of Nipah virus fusion (F) glycoprotein trimer by targeting the oligomerization sites used to form the functional hexamer-of-trimer assembly. Coupled with their dynamic stability and favorable ADMET profiles in both human and swine conditions, these findings make them good candidates for subsequent in vitro testing and further biological screening in the quest for potent antiviral drugs targeting Nipah virus proteins.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876403","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

Correction.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-22 DOI: 10.1080/07391102.2024.2444746

引用次数: 0

Evolution-based protein engineering: functional switching between transthyretins and 5-hydroxyisourate hydrolases.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-20 DOI: 10.1080/07391102.2024.2440647

Rafael Pereira Lemos, Julia T Rodrigues, Gabriel Portwood, Lucas Carrijo de Oliveira, Paulo Henrique Gomes Dos Santos, Mariana Amália Figueiredo Costa, Humberto D'Muniz Pereira, Lucas Bleicher, Mariana T Q de Magalhães

{"title":"Evolution-based protein engineering: functional switching between transthyretins and 5-hydroxyisourate hydrolases.","authors":"Rafael Pereira Lemos, Julia T Rodrigues, Gabriel Portwood, Lucas Carrijo de Oliveira, Paulo Henrique Gomes Dos Santos, Mariana Amália Figueiredo Costa, Humberto D'Muniz Pereira, Lucas Bleicher, Mariana T Q de Magalhães","doi":"10.1080/07391102.2024.2440647","DOIUrl":"https://doi.org/10.1080/07391102.2024.2440647","url":null,"abstract":"Transthyretin (TTR) is a vertebrate-exclusive transport protein that plays a key role in binding and distributing thyroid hormones. However, its evolutionary origin lies in the duplication of the gene that encoding the enzyme 5-hydroxyisourate hydrolase (HIUase), which is involved in uric acid metabolism. Unlike TTR, HIUase is ubiquitous in both prokaryotes and eukaryotes, with the exception of hominids. Both HIUase and TTR subfamilies form homotetramers, possessing an internal charged cavity between the two dimer pairs. Based on their high degree of structural similarity, we hypothesized that specific in silico substitutions would enable the interconversion between these protein functions. Using an evolution-based approach, we engineered two putative protein sequences, where correlated locally conserved positions from one subfamily representative sequence were substituted by the other, and vice versa. Applying computational modeling techniques, the best models were refined, validated, and their cavity volumes, three-dimensional geometries, propensity to aggregation and electrostatic potentials were analyzed. Molecular dynamics simulations were performed with the reference proteins and the engineered mutants in the bound and unbound states. We demonstrate that the volumes and geometries differ from one another, due to size and physicochemical differences between their ligands. The bound state mutant complexes are stable, and the enzymatic assay demonstrated active new enzymes. Our work suggests that the evolution-based protein engineering approach used has residue-specific resolution to identify locally conserved residues in the sequence of evolutionarily related proteins, such as HIUase and TTR.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864297","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

In silico screening of dicoumarols as potential Mur B enzyme inhibitors in Mycobacterium tuberculosis: molecular docking, ADME, QSAR and MD simulations.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-20 DOI: 10.1080/07391102.2024.2443126

Mansi, Pankaj Khanna, Shilpa Yadav, Asmita Singh, Leena Khanna

{"title":"In silico screening of dicoumarols as potential Mur B enzyme inhibitors in Mycobacterium tuberculosis: molecular docking, ADME, QSAR and MD simulations.","authors":"Mansi, Pankaj Khanna, Shilpa Yadav, Asmita Singh, Leena Khanna","doi":"10.1080/07391102.2024.2443126","DOIUrl":"https://doi.org/10.1080/07391102.2024.2443126","url":null,"abstract":"UDP-N-acetylenolpyruvoylglucosamine reductase (Mur B) from Mycobacterium tuberculosis has gathered significant pharmaceutical interest as a pivotal target because of its essential role in bacterial viability. This study employed computational methods to screen and assess the inhibitory potential of dicoumarol derivatives against the Mur B protein. A diverse set of dicoumarols, sourced from PubChem and Zinc database, is subjected to molecular docking, ADME studies, and MD simulations to elucidate interacting modes and stability. A QSAR model was constructed for dicoumarol derivatives based on known inhibitor MIC values against Staphylococcus aureus and Mur B. The four best dicoumarols (CID142097979, CID54716867, CID91962283, CID54705236) aligned well with the model. Subsequently, these dicoumarols were scrutinized via 200 ns MD simulations and MM-PBSA analysis to assess their complex stability with Mur B protein. Various MD simulation parameters such as RMSD, RMSF, Rg, H-bonds, PCA, and FEL were employed. The 200 ns MD simulation analysis outcomes indicated that the Mur B-CID54705236 complex exhibited the highest stability and possessed the binding energy of -59.96 kcal/mol further verifying its stability. The post-dynamic simulation analysis showed four hydrogen bond formations with Ser70, Asn71, Leu72 and Gln137 residues at the active site of Mur B. Overall, these results underscored dicoumarol derivatives as potential Mur B inhibitors and these findings can serve as a basis for further in vitro studies against Mur B protein.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869382","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

Inhibiting brushite crystal growth: molecular docking exploration of Enhydra fluctuans phytoconstituents and their interaction with human serum albumin.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-20 DOI: 10.1080/07391102.2024.2442761

Arijit Nandi, Bornika Chattaraj, Anwesha Das, Rammani Prasad, Yadu Nandan Dey

{"title":"Inhibiting brushite crystal growth: molecular docking exploration of Enhydra fluctuans phytoconstituents and their interaction with human serum albumin.","authors":"Arijit Nandi, Bornika Chattaraj, Anwesha Das, Rammani Prasad, Yadu Nandan Dey","doi":"10.1080/07391102.2024.2442761","DOIUrl":"https://doi.org/10.1080/07391102.2024.2442761","url":null,"abstract":"In our preliminary in vitro studies, the Enhydra fluctuans extract demonstrated inhibition of calcium phosphate (brushite) crystals. Human serum albumin (HSA) is known to act as a promoter of brushite crystal growth. Therefore, the present study aims to explore the molecular mechanisms involved in brushite crystal nephrolithiasis by conducting molecular docking of phytoconstituents from E. fluctuans with HSA. Molecular docking is conducted on 35 phytoconstituents of E. fluctuans against HSA, and the top five compounds are further analyzed using Induced Fit Docking (IFD) and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) methods. Molecular dynamics simulations for 50 ns are performed to assess the stability of the protein-ligand complexes. Additionally, in silico physicochemical; absorption, distribution, metabolism, excretion, and toxicity (ADME/T); and pharmacophore modeling studies are conducted. The binding pocket analysis identifies potential binding sites on HSA, and molecular docking reveals Baicalein-7-o-glucoside as the top-performing compound with a strong binding affinity. IFD and MM-GBSA support the stability of the complex. Molecular dynamics simulations indicate stable interactions over the 50 ns period. In silico ADME/T studies suggest that the top five phytoconstituents exhibit drug-like properties with satisfactory pharmacokinetic profiles. Pharmacophore modeling generates a three-point hypothesis, and its validation indicates suitability for the HSA-Baicalein-7-O-glucoside complex. The findings from the current computational investigations indicate that polyphenolic phytoconstituents of E. fluctuans containing the 5,6-dihydroxy chromone ring, such as Baicalein-7-O-diglucoside, may modulate the activity of HSA (PDB ID: 1E7H), potentially inhibiting the process of crystallization.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864314","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

Decoding the in-silico structure of isopentenyl Diphosphate Delta-Isomerase protein from Cassia angustifolia Vahl.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-12-20 DOI: 10.1080/07391102.2024.2442757

Khushali Thaker, Jaimini Patoliya, Jignesh Prajapati, Khushbu Rabadiya, Manivel Ponnuchamy, Rakesh Rawal, Nagaraja Reddy Rama Reddy, Rushikesh Joshi

{"title":"Decoding the in-silico structure of isopentenyl Diphosphate Delta-Isomerase protein from Cassia angustifolia Vahl.","authors":"Khushali Thaker, Jaimini Patoliya, Jignesh Prajapati, Khushbu Rabadiya, Manivel Ponnuchamy, Rakesh Rawal, Nagaraja Reddy Rama Reddy, Rushikesh Joshi","doi":"10.1080/07391102.2024.2442757","DOIUrl":"https://doi.org/10.1080/07391102.2024.2442757","url":null,"abstract":"Senna (Cassia angustifolia Vahl.) is an important medicinal plant used in traditional and modern systems medicine to manage constipation. While various treatment strategies exist, there is growing interest in utilizing traditional herbal medicines like Indian Senna as a natural alternative. Though Isopentenyl Diphosphate Delta-Isomerase (IDI) has been proven to be one of the key enzymes in the sennoside biosynthesis pathway, characterization of it remains largely unexplored. This study aims to bridge the knowledge gap by investigating IDI, an important enzyme involved in sennoside biosynthesis in plants. The study retrieved the coding DNA sequence (CDS) of IDI from Senna transcriptome and successfully cloned and sequenced the gene. Physicochemical properties and secondary structure analysis unveiled protein characteristics, while homology modelling and molecular docking of DMAPP and IPP ligands assessed binding patterns and interactions with caIDI. Notably, Lys37, Arg72, Lys76, Cys88, Ser89, His90, and Lys113 residues engaged with DMAPP, and Arg72, Lys76, Lys113, Ser89, and His90 residues interacted with IPP. Molecular dynamics simulations affirmed protein-ligand complex stability. IPP established sustained hydrogen bonds with Arg72, Ser89, and Lys113; DMAPP sustained interactions with Lys37, Arg72, Ser89, His90 and Lys113. His41, Glu148, Glu150 engaged with magnesium ion; Val77, Thr78 showed dual interactions with IPP, indicating its substrate binding roles. These findings enhance IDI understanding in Indian Senna which not only plays vital role in isoprenoid biosynthesis but also anthraquinone biosynthesis like sennosides.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864295","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