Proteins-Structure Function and Bioinformatics最新文献_第3页

Structure, Oligomerization, and Thermal Stability of a Recently Discovered Old Yellow Enzyme. 一种新发现的古老黄色酶的结构、寡聚和热稳定性。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-22 DOI: 10.1002/prot.26800

Nakia Polidori, Peter Babin, Bastian Daniel, Karl Gruber

引用次数: 0

Exploring the Conformational Space of MPS1 Kinase Using Metadynamics. 用元动力学方法研究MPS1激酶的构象空间。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-09 DOI: 10.1002/prot.26796

Anuradha Singh, Naga Rajiv Lakkaniga

引用次数: 0

DisDock: A Deep Learning Method for Metal Ion-Protein Redocking. DisDock：一种金属离子-蛋白质再对接的深度学习方法。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-22 DOI: 10.1002/prot.26791

Menghan Lin, Keqiao Li, Yuan Zhang, Feng Pan, Wei Wu, Jinfeng Zhang

{"title":"DisDock: A Deep Learning Method for Metal Ion-Protein Redocking.","authors":"Menghan Lin, Keqiao Li, Yuan Zhang, Feng Pan, Wei Wu, Jinfeng Zhang","doi":"10.1002/prot.26791","DOIUrl":"10.1002/prot.26791","url":null,"abstract":"The structures of metalloproteins are essential for comprehending their functions and interactions. The breakthrough of AlphaFold has made it possible to predict protein structures with experimental accuracy. However, the type of metal ion that a metalloprotein binds and the binding structure are still not readily available, even with the predicted protein structure. In this study, we present DisDock, a deep learning method for predicting protein-metal docking. DisDock takes distogram of randomly initialized protein-ligand configuration as input and outputs the distogram of the predicted binding complex. It combines the U-net architecture with self-attention modules to enhance model performance. Taking inspiration from the physical principle that atoms in closer proximity display a stronger mutual attraction, this predictor capitalizes on geometric information to uncover latent characteristics indicative of atom interactions. To train our model, we employ a high-quality metalloprotein dataset sourced from the Mother of All Databases (MOAD). Experimental results demonstrate that our approach outperforms other existing methods in prediction accuracy for various types of metal ions.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1171-1180"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Unraveling the Molecular Architecture of Mosquito D1-Like Dopamine Receptors: Insights Into Ligand Binding and Structural Dynamics for Insecticide Development. 揭示蚊子d1样多巴胺受体的分子结构：对配体结合和杀虫剂开发结构动力学的见解。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-18 DOI: 10.1002/prot.26783

Subrata Dasgupta, Prasenjit Bhaumik

{"title":"Unraveling the Molecular Architecture of Mosquito D1-Like Dopamine Receptors: Insights Into Ligand Binding and Structural Dynamics for Insecticide Development.","authors":"Subrata Dasgupta, Prasenjit Bhaumik","doi":"10.1002/prot.26783","DOIUrl":"10.1002/prot.26783","url":null,"abstract":"Vector-borne diseases pose a severe threat to human life, contributing significantly to global mortality. Understanding the structure-function relationship of the vector proteins is pivotal for effective insecticide development due to their involvement in drug resistance and disease transmission. This study reports the structural and dynamic features of D1-like dopamine receptors (DARs) in disease-causing mosquito species, such as Aedes aegypti , Culex quinquefasciatus , Anopheles gambiae , and Anopheles stephensi. Through molecular modeling and simulations, we describe the common structural fold of mosquito DARs within the G-protein-coupled receptor family, highlighting the importance of an orthosteric and enlarged binding pocket. The orthosteric binding pocket, resembling a cage-like structure, is situated ~15 Å deep within the protein, with two serine residues forming the roof and an aspartate residue, along with two conserved water molecules (W1 and W2), forming the floor. The side walls are composed of two phenylalanine residues on one side and a valine residue on the other. The antagonist binding site, an enlarged binding pocket (EBP) near the entrance cavity, can accommodate ligands of varying sizes. The binding energy of dopamine is observed to be ~2-3 kcal/mol higher than that of the antagonist molecules amitriptyline, asenapine, and flupenthixol in mosquito DARs. These antagonist molecules bind to EBP, which obstructs dopamine movement toward the active site, thereby inhibiting signal transduction. Our findings elucidate the molecular architecture of the binding pockets and the versatility of DARs in accommodating diverse ligands, providing a foundational framework for future drug and insecticide development.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1157-1170"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Structure of the Complex of Lactoperoxidase With Nitric Oxide at 1.95 Å Resolution. 乳酸过氧化物酶与一氧化氮复合物在1.95 Å分辨率下的结构。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-02 DOI: 10.1002/prot.26797

Ankit Maurya, Nabeel Ahmad, Pradeep Sharma, Sujata Sharma, T P Singh

{"title":"Structure of the Complex of Lactoperoxidase With Nitric Oxide at 1.95 Å Resolution.","authors":"Ankit Maurya, Nabeel Ahmad, Pradeep Sharma, Sujata Sharma, T P Singh","doi":"10.1002/prot.26797","DOIUrl":"10.1002/prot.26797","url":null,"abstract":"Lactoperoxidase (LPO) is a heme-containing mammalian enzyme that is found in the extracellular fluids of animals including plasma, saliva, airway epithelial and nasal lining fluids, milk, tears, and gastric juices. LPO uses hydrogen peroxide (H2O2) to convert substrates into oxidized products. Previous structural studies have shown that H2O2, CO, and CN are bound to LPO at the distal heme cavity by coordinating with heme iron. The structure of the complex of LPO with NO shows that NO also binds to LPO at the distal heme cavity and forms a coordinate linkage with heme iron. The structure shows that the nitrogen atom of NO is linked to heme iron at a distance of 1.97 while the oxygen atom is attached to the Nε2 atom of His109 at a distance of 2.23 Å. On the other hand, N atom of NO is located with an interatomic distance of 3.25 Å allowing a hydrogen-bonding interaction with the Nε2 atom of Gln105. A comparison of the bindings of NO, CO, CN, and H2O2 in coordination with heme iron indicates stereochemical compatibility of the distal heme cavity for the binding of diatomic molecules. However, notable differences are observed in their orientations in the distal heme cavity indicating functional differences. The bindings of NO, CO, and CN by coordinating with heme iron result in the inhibition of LPO while the binding of H2O2 to heme iron produces an intermediate of LPO known as Compound I.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1079-1089"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

DeepUSPS: Deep Learning-Empowered Unconstrained-Structural Protein Sequence Design. DeepUSPS：基于深度学习的无约束结构蛋白序列设计。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-30 DOI: 10.1002/prot.26847

Zhichong Ma, Jiawen Yang

{"title":"DeepUSPS: Deep Learning-Empowered Unconstrained-Structural Protein Sequence Design.","authors":"Zhichong Ma, Jiawen Yang","doi":"10.1002/prot.26847","DOIUrl":"https://doi.org/10.1002/prot.26847","url":null,"abstract":"Currently, the unconstrained-structural protein sequence design models suffer from low optimization efficiency, and their generated proteins exhibit significant similarities to natural proteins and low thermal stability. To address these challenges, we propose the Deep Learning-Empowered Unconstrained-Structural Protein Sequence Design (DeepUSPS) model. To effectively address the inadequate thermal stability problem, we employ the innovative Inverted Dense Residual Network (IDRNet). To mitigate the designed proteins similarity issue, the Sequence-Pairwise Features Extraction Synthetic Network (SPFESN) is constructed. Furthermore, we introduce the Warm Restart AngularGrad (WRA) optimizer to optimize the 3D Position-Specific Scoring Matrix (3Dpssm) for unconstrained-structural protein sequence, only involving 2100 iterations (140.36 min) updates to generate idealization (IDE) protein sequences. We obtained a total of 1000 IDE protein sequences. Then we utilized in silico experiments to evaluate them, including similarity, clarity and iterations, thermal stability, spatial distribution of similarity, and predicted local-distance difference test (pLDDT) confidence assessment. Notably, the mean lg(E-value) for IDE protein sequences reached -0.051, the mean TM-score for IDE protein structures reached 0.594, the iterations only need 2100, and the mean Tm (melting point) for thermal stability reached 74.78°C. The average pLDDT value for 3D structures reached 76. Additionally, the IDE proteins' 3D structures exhibit diverse types. These in silico results conclusively demonstrate the superior performance of DeepUSPS compared with Hallucinate.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Insights Into the Dynamic Conformational Transitions and Active Site Plasticity of Human Immunoregulatory Cathepsin S. 人免疫调节组织蛋白酶S动态构象转变和活性位点可塑性的新见解。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-26 DOI: 10.1002/prot.26845

Durga Geetha, B A Aysha Hameeda, Deepthi Jose, Nishamol Kuriakose, Tom Skaria

{"title":"Novel Insights Into the Dynamic Conformational Transitions and Active Site Plasticity of Human Immunoregulatory Cathepsin S.","authors":"Durga Geetha, B A Aysha Hameeda, Deepthi Jose, Nishamol Kuriakose, Tom Skaria","doi":"10.1002/prot.26845","DOIUrl":"https://doi.org/10.1002/prot.26845","url":null,"abstract":"Cathepsin S (CatS), a cysteine protease, catalyzes the cleavage of immunoregulatory peptides and mediates tissue destruction in autoimmune and inflammatory diseases. Plasticity of its ligand binding site and mechanisms of dynamic transitions between different conformational states are critical in drug discovery; however, knowledge of its entire conformational landscape and transition mechanisms remains incomplete. Therefore, we investigated the atomic-level interactions between active site cleft residues that contribute to its structural and functional plasticity. Here, we show that the hinge movement of side chains of Phe211, Phe70, and Tyr118, followed by side chain reorientation of active site residues and inter-residue interactions, results in open or closed conformations, contributing to the plasticity of the S2 binding affinity hotspot pocket of CatS. Hinge movements of Phe211, Phe70, and Tyr118 regulate the space available in the S2 pocket, with Phe70 acting as a key regulator, thereby affecting small molecule binding in the active site cleft. Further, the non-covalent interactions between active site residues during transitions between open and closed states lead to the formation of three distinct, dynamic, semi-closed substates. The transition to the closed state can be blocked by a ligand that sterically hinders the hinge movement of Phe70 or Phe211. The cooperative, organized side chain rotation of Phe211, Phe70, and Tyr118, and subsequent emergence of non-covalent interactions between the active site residues can influence the accommodation of ligands and their specificity. These novel findings might further aid the design of selective small molecule drugs targeting specific conformational states of the immunoregulatory and inflammatory/autoimmune disease target human CatS.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Case Studies of Orphan Domain Reclassification in ECOD by Expert Curation. 基于专家策展的ECOD孤儿域重分类案例研究

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-26 DOI: 10.1002/prot.26840

Jimin Pei, R Dustin Schaeffer, Qian Cong, Nick V Grishin

{"title":"Case Studies of Orphan Domain Reclassification in ECOD by Expert Curation.","authors":"Jimin Pei, R Dustin Schaeffer, Qian Cong, Nick V Grishin","doi":"10.1002/prot.26840","DOIUrl":"https://doi.org/10.1002/prot.26840","url":null,"abstract":"Homology-based protein domain classification is a powerful tool for gaining biological insights into protein function. This classification process has been significantly enhanced by the availability of experimental structures and high-accuracy structural models generated by advanced tools such as AlphaFold. Our Evolutionary Classification of protein Domains (ECOD) database provides a continuously updated and refined domain classification system. Isolated (\"orphan\") protein domain families, which have a limited distribution in the protein universe, present a unique challenge in this classification process. These families lack clear or identifiable evolutionary relationships with other sequence families. While some isolated domain families may have emerged through de novo evolution, others potentially share common evolutionary origins with existing domain families but represent difficult cases for traditional classification methods. In this study, we conducted a manual analysis of a set of isolated families of small domains in ECOD. By exploring sequence, structural, and functional evidence, we uncovered distant members and likely homologous relationships between different isolated domain families that were previously unrecognized. Our analysis provides valuable insights into the evolution of isolated domain families and has led to improved classification within ECOD. This work enhances our understanding of protein evolution and underscores the importance of continuous refinement in domain classification systems as new data and analytical methods become available.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

REV-ERBβ Binding Pocket Dynamics With Implications for Rational Design of Small Molecule Modulators. REV-ERBβ结合袋动力学及其对小分子调节剂合理设计的启示。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-26 DOI: 10.1002/prot.26841

Shriyansh Srivastava, A M Vishnu, Rakesh Thakur, Ashutosh Srivastava

{"title":"REV-ERBβ Binding Pocket Dynamics With Implications for Rational Design of Small Molecule Modulators.","authors":"Shriyansh Srivastava, A M Vishnu, Rakesh Thakur, Ashutosh Srivastava","doi":"10.1002/prot.26841","DOIUrl":"https://doi.org/10.1002/prot.26841","url":null,"abstract":"REV-ERBβ is a nuclear receptor (NR) with heme as an endogenous ligand that regulates its transcriptional activity. With a key role in cellular functions such as glucose metabolism, immune response, and dysregulation in pathologies such as Type-2 diabetes mellitus and obesity, small molecule agonists and antagonists targeting REV-ERBs have been discovered. However, due to a lack of crystal structures in complex with these compounds, the structural and dynamical basis of these activities still remains elusive and hinders the rational design of molecules targeting REV-ERB. Using molecular dynamics simulations and docking studies, we have characterized the dynamics of REV-ERBβ ligand-binding domain (LBD) in different conformational states. The presence of heme in the binding pocket within LBD was found to dampen its dynamics as well as nuclear co-repressor (NCoR) peptide binding. We further show that the binding of the antagonist destabilizes the NCoR peptide binding to LBD mediated by loss of interactions with residues at the NCoR-REV-ERBβ interface. These findings could be utilized to design molecular scaffolds with better activity and selectivity against REV-ERBβ.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Fusion Protein-Assisted Crystallization of Human SUMO1. 融合蛋白辅助人SUMO1的结晶。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-23 DOI: 10.1002/prot.26838

Aanchal Mishra, Stéphane Goffinont, Franck Coste, El Hadji Cisse, Lucija Mance, Bertrand Castaing, Marcin J Suskiewicz

{"title":"Fusion Protein-Assisted Crystallization of Human SUMO1.","authors":"Aanchal Mishra, Stéphane Goffinont, Franck Coste, El Hadji Cisse, Lucija Mance, Bertrand Castaing, Marcin J Suskiewicz","doi":"10.1002/prot.26838","DOIUrl":"https://doi.org/10.1002/prot.26838","url":null,"abstract":"In this study, we employed a fusion protein-assisted approach to crystallize human SUMO1, an essential covalent protein modifier that also interacts noncovalently with specific linear protein motifs called SUMO-interacting motifs (SIMs). SUMO1 has been crystallized previously as part of various complexes but never in isolation. Our strategy involved fusing a variant of a known crystallization facilitator, the TELSAM domain, upstream of the folded part of the SUMO1 protein (residues 18-97). Following a simple purification strategy, we obtained a 2.05-Å crystal structure of apo TELSAM-SUMO1, with three distinct SUMO1 chains per asymmetric unit, two of which have an accessible pocket for binding to a SIM. The crystal structure is composed of the expected left-handed helical filaments formed by TELSAM domains, with protruding SUMO1 molecules mediating connections within and between these filaments to stabilize a three-dimensional lattice. Since the TELSAM fusion does not affect the SUMO:SIM interaction, as confirmed in solution, our construct may potentially be used to structurally characterize complexes formed between SUMO and SIM-containing peptides. Neither does the TELSAM fusion interfere with the attachment of SUMO1 to substrates, potentially allowing for the creation of SUMOylated protein forms with improved crystallizability. The study represents a novel application of TELSAM-assisted crystallization to a small protein of major biological relevance.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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