Current Research in Structural Biology最新文献

{"title":"Integrative modeling of JCVI-Syn3A nucleoids with a modular approach","authors":"David S. Goodsell ,&nbsp;Ludovic Autin","doi":"10.1016/j.crstbi.2023.100121","DOIUrl":"10.1016/j.crstbi.2023.100121","url":null,"abstract":"<div><p>A lattice-based method is presented for creating 3D models of entire bacterial nucleoids integrating ultrastructural information cryoelectron tomography, genomic and proteomic data, and experimental atomic structures of biomolecules and assemblies. The method is used to generate models of the minimal genome bacterium JCVI-Syn3A, producing a series of models that test hypotheses about transcription, condensation, and overall distribution of the genome. Lattice models are also used to generate atomic models of an entire JCVI-Syn3A cell.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100121"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X23000272/pdfft?md5=2b6046ee7971c557a79d6bdb88434d6f&pid=1-s2.0-S2665928X23000272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139019360","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}

{"title":"Bacterial selenocysteine synthase structure revealed by single-particle cryoEM","authors":"Vitor Hugo Balasco Serrão ,&nbsp;Karine Minari ,&nbsp;Humberto D'Muniz Pereira ,&nbsp;Otavio Henrique Thiemann","doi":"10.1016/j.crstbi.2024.100143","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100143","url":null,"abstract":"<div><p>The 21st amino acid, selenocysteine (Sec), is synthesized on its dedicated transfer RNA (tRNA^Sec). In bacteria, Sec is synthesized from Ser-tRNA^[Ser]Sec by Selenocysteine Synthase (SelA), which is a pivotal enzyme in the biosynthesis of Sec. The structural characterization of bacterial SelA is of paramount importance to decipher its catalytic mechanism and its role in the regulation of the Sec-synthesis pathway. Here, we present a comprehensive single-particle cryo-electron microscopy (SPA cryoEM) structure of the bacterial SelA with an overall resolution of 2.69 Å. Using recombinant <em>Escherichia coli</em> SelA, we purified and prepared samples for single-particle cryoEM. The structural insights from SelA, combined with previous <em>in vivo</em> and <em>in vitro</em> knowledge, underscore the indispensable role of decamerization in SelA's function. Moreover, our structural analysis corroborates previous results that show that SelA adopts a pentamer of dimers configuration, and the active site architecture, substrate binding pocket, and key K295 catalytic residue are identified and described in detail. The differences in protein architecture and substrate coordination between the bacterial enzyme and its counterparts offer compelling structural evidence supporting the independent molecular evolution of the bacterial and archaea/eukarya Ser-Sec biosynthesis present in the natural world.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100143"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000205/pdfft?md5=61e3be36dda3b09031c6347f51a91207&pid=1-s2.0-S2665928X24000205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558413","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}

{"title":"Pathogenic single nucleotide polymorphisms in RhoA gene: Insights into structural and functional impacts on RhoA-PLD1 interaction through molecular dynamics simulation","authors":"Mahbub Hasan ,&nbsp;Md. Nayem Sarker ,&nbsp;Tazkia Jabin ,&nbsp;Saifuddin Sarker,&nbsp;Shamim Ahmed,&nbsp;Mohammad Abdullah-Al-Shoeb,&nbsp;Tanvir Hossain","doi":"10.1016/j.crstbi.2024.100159","DOIUrl":"10.1016/j.crstbi.2024.100159","url":null,"abstract":"<div><div>Molecular switches serve as key regulators of biological systems by acting as one of the crucial driving forces in the initiation of signal transduction pathway cascades. The Ras homolog gene family member A (RhoA) is one of the molecular switches that binds with GTP in order to cycle between an active GTP-bound state and an inactive GDP-bound state. Any aberrance in control over this circuit, particularly due to any perturbation in switching, leads to the development of different pathogenicity. Consequently, the single nucleotide polymorphisms (SNPs) within the RhoA gene, especially deleterious genetic variations, are crucial to study to forecast structural alteration and their functional impacts in light of disease onset. In this comprehensive study, we employed a range of computational tools to screen the deleterious SNPs of RhoA from 207 nonsynonymous SNPs (nsSNPs). By utilizing 7 distinct tools for further analysis, 8 common deleterious SNPs were sorted, among them 5 nsSNPs (V9G, G17E, E40K, A61T, F171L) were found to be in the highly conserved regions, with E40K and A61T at G2 and G3 motif of the GTP-binding domain respectively, indicating potential perturbation in GTP/GDP binding ability of the protein. RhoA-GDP complex interacts with the enzyme phospholipase, specifically PLD1, to regulate different cellular activities. PLD1 is also a crucial regulator of thrombosis and cancer. In that line of focus, our initial structural analysis of Y66H, A61T, G17E, I86N, and I151T mutations of RhoA revealed remarkable decreased hydrophobicity from which we further filtered out G17E and I86N which may have potential impact on the RhoA-GDP-PLD1 complex. Intriguingly, the comparative 250 ns (ns) molecular dynamics (MD) simulation of these two mutated complexes revealed overall structural instability and altered interaction patterns. Therefore, further investigation into these deleterious mutations with <em>in vitro</em> and <em>in vivo</em> studies could lead to the identification of potential biomarkers in terms of different pathogenesis and could also be utilized in personalized therapeutic targets in the long run.</div></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"8 ","pages":"Article 100159"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853227","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}

{"title":"Identification of coumarin derivatives targeting acetylcholinesterase for Alzheimer's disease by field-based 3D-QSAR, pharmacophore model-based virtual screening, molecular docking, MM/GBSA, ADME and MD Simulation study","authors":"Bikram Saha ,&nbsp;Agnidipta Das ,&nbsp;Kailash Jangid ,&nbsp;Amit Kumar ,&nbsp;Vinod Kumar ,&nbsp;Vikas Jaitak","doi":"10.1016/j.crstbi.2024.100124","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100124","url":null,"abstract":"<div><p>Alzheimer's disease (AD) leads to gradual memory loss including other compromised cognitive abilities. Acetylcholinesterase (AChE), an important biochemical enzyme from the cholinesterase (ChE) family, is recognized as primary pharmacological target for treating AD. Currently marketed drugs for AD treatment are primarily AChE inhibitors and coumarin derivatives comprising a wide variety of pharmacological activities have proved their efficacy towards AChE inhibition. Ensaculin (KA-672 HCl), a compound that belong to the coumarin family, is a clinical trial candidate for AD treatment. Therefore, a ligand library was prepared with 60 reported coumarin derivatives for field-based 3D-QSAR and pharmacophore modelling. The field-based 3D-QSAR model obtained at partial least square (PLS) factor 7, was the best validated model that predicted activity closer to original activity for each ligand introduced. The contour maps demonstrated spatial distribution of favourable and unfavorable steric, hydrophobic, electrostatic and H-bond donor and acceptor contours around coumarin nucleus. The best pharmacophore model, ADHRR_1 exhibited five essential pharmacophoric features of four different traits for optimum AChE inhibition. Virtual screening through ADHRR_1 accompanied with molecular docking and MM/GBSA identified 10 HITs from a 4,00,000 coumarin derivatives from PubChem database. HITs comprised docking scores ranging from −12.096 kcal/mol to −8.271 kcal/mol and compared with the reference drug Donepezil (-8.271 kcal/mol). ADME properties analysis led into detecting two leads (HIT 1 and HIT 2) among these 10 HITs. Molecular Dynamics Simulation indicated thermodynamic stability of the complex of lead compounds with AChE protein. Finally, thorough survey of the experimental results from 3D-QSAR modelling, pharmacophore modelling and molecular docking interactions led us to develop the lead formula I for future advancements in treating AD through AChE inhibitors.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100124"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000011/pdfft?md5=0302117bf96bd14c51a89e51e6661f84&pid=1-s2.0-S2665928X24000011-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139433557","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}

{"title":"Alternate conformations found in protein structures implies biological functions: A case study using cyclophilin A","authors":"Chandrasekaran Palaniappan ,&nbsp;Santhosh Rajendran ,&nbsp;Kanagaraj Sekar","doi":"10.1016/j.crstbi.2024.100145","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100145","url":null,"abstract":"<div><p>Protein dynamics linked to numerous biomolecular functions, such as ligand binding, allosteric regulation, and catalysis, must be better understood at the atomic level. Reactive atoms of key residues drive a repertoire of biomolecular functions by flipping between alternate conformations or conformational substates, seldom found in protein structures. Probing such sparsely sampled alternate conformations would provide mechanistic insight into many biological functions. We are therefore interested in evaluating the instance of amino acids adopted alternate conformations, either in backbone or side-chain atoms or in both. Accordingly, over 70000 protein structures appear to contain alternate conformations only 'A' and 'B' for any atom, particularly the instance of amino acids that adopted alternate conformations are more for Arg, Cys, Met, and Ser than others. The resulting protein structure analysis depicts that amino acids with alternate conformations are mainly found in the helical and β-regions and are often seen in high-resolution X-ray crystal structures. Furthermore, a case study on human cyclophilin A (CypA) was performed to explain the pre-existing intrinsic dynamics of catalytically critical residues from the CypA and how such intrinsic dynamics perturbed upon Ser99Thr mutation using molecular dynamics simulations on the ns-μs timescale. Simulation results demonstrated that the Ser99Thr mutation had impaired the alternate conformations or the catalytically productive micro-environment of Phe113, mimicking the experimentally observed perturbation captured by X-ray crystallography. In brief, a deeper comprehension of alternate conformations adopted by the amino acids may shed light on the interplay between protein structure, dynamics, and function.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100145"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000229/pdfft?md5=99f78944ded3d8b7139bf3f324f58946&pid=1-s2.0-S2665928X24000229-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638479","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}

{"title":"Structure and function of the light-protective orange carotenoid protein families","authors":"Teresa M. García-Oneto ,&nbsp;Claudia Moyano-Bellido ,&nbsp;M. Agustina Domínguez-Martín","doi":"10.1016/j.crstbi.2024.100141","DOIUrl":"10.1016/j.crstbi.2024.100141","url":null,"abstract":"<div><p>Orange carotenoid proteins (OCPs) are unique photoreceptors that are critical for cyanobacterial photoprotection. Upon exposure to blue-green light, OCPs are activated from a stable orange form, OCP^O, to an active red form, OCP^R, which binds to phycobilisomes (PBSs) and performs photoprotective non-photochemical quenching (NPQ). OCPs can be divided into three main families: the most abundant and best studied OCP1, and two others, OCP2 and OCP3, which have different activation and quenching properties and are yet underexplored. Crystal structures have been acquired for the three OCP clades, providing a glimpse into the conformational underpinnings of their light-absorption and energy dissipation attributes. Recently, the structure of the PBS-OCP^R complex has been obtained allowing for an unprecedented insight into the photoprotective action of OCPs. Here, we review the latest findings in the field that have substantially improved our understanding of how cyanobacteria protect themselves from the toxic consequences of excess light absorption. Furthermore, current research is applying the structure of OCPs to bio-inspired optogenetic tools, to function as carotenoid delivery devices, as well as engineering the NPQ mechanism of cyanobacteria to enhance their photosynthetic biomass production.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100141"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000187/pdfft?md5=94fcdc3bbbf23bc37abf0f283dfea5e5&pid=1-s2.0-S2665928X24000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757478","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}

{"title":"Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir","authors":"S.V. Sankaran ,&nbsp;Sowmya R. Krishnan ,&nbsp;Yasien Sayed ,&nbsp;M. Michael Gromiha","doi":"10.1016/j.crstbi.2024.100132","DOIUrl":"10.1016/j.crstbi.2024.100132","url":null,"abstract":"<div><p>AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100132"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000096/pdfft?md5=306b72342c5038d99b11a59449839fde&pid=1-s2.0-S2665928X24000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139966445","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}

{"title":"Structure-function analyses reveal Arabidopsis thaliana HDA7 to be an inactive histone deacetylase","authors":"Ketul Saharan ,&nbsp;Somanath Baral ,&nbsp;Nausad Hossain Shaikh ,&nbsp;Dileep Vasudevan","doi":"10.1016/j.crstbi.2024.100136","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100136","url":null,"abstract":"<div><p>Histone deacetylases (HDACs), responsible for the removal of acetyl groups from histone tails, are important epigenetic factors. They play a critical role in the regulation of gene expression and are significant in the context of plant growth and development. The Rpd3/Hda1 family of HDACs is reported to regulate key biological processes in plants, such as stress response, seed, embryonic, and floral development. Here, we characterized <em>Arabidopsis thaliana</em> HDA7, a Class I, Rpd3/Hda1 family HDAC. SAXS and AUC results show that the recombinantly expressed and purified histone deacetylase domain of AtHDA7 exists as a monomer in solution. Further, the crystal structure showed AtHDA7 to fold into the typical α/β arginase fold, characteristic of Rpd3/Hda1 family HDACs. Sequence analysis revealed that the Asp and His residues of the catalytic ‘XDXH’ motif present in functional Rpd3/Hda1 family HDACs are mutated to Gly and Pro, respectively, in AtHDA7, suggesting that it might be catalytically inactive. The Asp and His residues are important for Zn²⁺-binding. Not surprisingly, the crystal structure did not have Zn²⁺ bound in the catalytic pocket, which is essential for the HDAC activity. Further, our <em>in vitro</em> activity assay revealed AtHDA7 to be inactive as an HDAC. A search in the sequence databases suggested that homologs of AtHDA7 are found exclusively in the Brassicaceae family to which Arabidopsis belongs. It is possible that HDA7 descended from HDA6 through whole genome duplication and triplication events during evolution, as suggested in a previous phylogenetic study.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100136"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000138/pdfft?md5=9613b556bf68eed37357f5c1262013ad&pid=1-s2.0-S2665928X24000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140014121","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}

{"title":"Experimental methods to study the structure and dynamics of intrinsically disordered regions in proteins","authors":"Snigdha Maiti ,&nbsp;Aakanksha Singh,&nbsp;Tanisha Maji,&nbsp;Nikita V. Saibo,&nbsp;Soumya De","doi":"10.1016/j.crstbi.2024.100138","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100138","url":null,"abstract":"<div><p>Eukaryotic proteins often feature long stretches of amino acids that lack a well-defined three-dimensional structure and are referred to as intrinsically disordered proteins (IDPs) or regions (IDRs). Although these proteins challenge conventional structure-function paradigms, they play vital roles in cellular processes. Recent progress in experimental techniques, such as NMR spectroscopy, single molecule FRET, high speed AFM and SAXS, have provided valuable insights into the biophysical basis of IDP function. This review discusses the advancements made in these techniques particularly for the study of disordered regions in proteins. In NMR spectroscopy new strategies such as ¹³C detection, non-uniform sampling, segmental isotope labeling, and rapid data acquisition methods address the challenges posed by spectral overcrowding and low stability of IDPs. The importance of various NMR parameters, including chemical shifts, hydrogen exchange rates, and relaxation measurements, to reveal transient secondary structures within IDRs and IDPs are presented. Given the high flexibility of IDPs, the review outlines NMR methods for assessing their dynamics at both fast (ps-ns) and slow (μs-ms) timescales. IDPs exert their functions through interactions with other molecules such as proteins, DNA, or RNA. NMR-based titration experiments yield insights into the thermodynamics and kinetics of these interactions. Detailed study of IDPs requires multiple experimental techniques, and thus, several methods are described for studying disordered proteins, highlighting their respective advantages and limitations. The potential for integrating these complementary techniques, each offering unique perspectives, is explored to achieve a comprehensive understanding of IDPs.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100138"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000151/pdfft?md5=f40c41eba2b2db9f84e2f421c05b2b24&pid=1-s2.0-S2665928X24000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140807179","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}

{"title":"GraSp-PSN: A web server for graph spectra based analysis of protein structure networks","authors":"Vasundhara Gadiyaram,&nbsp;Vasam Manjveekar Prabantu,&nbsp;Arinnia Anto Manjaly ,&nbsp;Ananth Muthiah,&nbsp;Saraswathi Vishveshwara","doi":"10.1016/j.crstbi.2024.100147","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100147","url":null,"abstract":"<div><p>The function of a protein is most of the time achieved due to minute conformational changes in its structure due to ligand binding or environmental changes or other interactions. Hence the analysis of structure of proteins should go beyond the analysis of mere atom contacts and should include the emergent global structure as a whole. This can be achieved by graph spectra based analysis of protein structure networks. GraSp-PSN is a web server that can assist in (1) acquiring weighted protein structure network (PSN) and network parameters ranging from atomic level to global connectivity from the three dimensional coordinates of a protein, (2) generating scores for comparison of a pair of protein structures with detailed information of local to global connectivity, and (3) assigning perturbation scores to the residues and their interactions, that can prioritise them in terms of residue clusters. The methods implemented in the server are generic in nature and can be used for comparing networks in any discipline by uploading adjacency matrices in the server. The webserver can be accessed using the following link: <span>https://pople.mbu.iisc.ac.in/</span><svg><path></path></svg>.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100147"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000242/pdfft?md5=739c6cab73a5919caa6cedc6fe5317c7&pid=1-s2.0-S2665928X24000242-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140879520","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}