Proteins-Structure Function and Bioinformatics最新文献_第2页

Massive Sampling Strategy for Antibody-Antigen Targets in CAPRI Round 55 With MassiveFold.

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-01-27 DOI: 10.1002/prot.26802

Nessim Raouraoua, Marc F Lensink, Guillaume Brysbaert

引用次数: 0

The Pseudoenzyme β-Amylase9 From Arabidopsis Activates α-Amylase3: A Possible Mechanism to Promote Stress-Induced Starch Degradation.

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-01-23 DOI: 10.1002/prot.26803

Christopher E Berndsen, Amanda R Storm, Angelina M Sardelli, Sheikh R Hossain, Kristen R Clermont, Luke M McFather, Mafe A Connor, Jonathan D Monroe

{"title":"The Pseudoenzyme β-Amylase9 From Arabidopsis Activates α-Amylase3: A Possible Mechanism to Promote Stress-Induced Starch Degradation.","authors":"Christopher E Berndsen, Amanda R Storm, Angelina M Sardelli, Sheikh R Hossain, Kristen R Clermont, Luke M McFather, Mafe A Connor, Jonathan D Monroe","doi":"10.1002/prot.26803","DOIUrl":"10.1002/prot.26803","url":null,"abstract":"Starch accumulation in plants provides carbon for nighttime use, for regrowth after periods of dormancy, and for times of stress. Both ɑ- and β-amylases (AMYs and BAMs, respectively) catalyze starch hydrolysis, but their functional roles are unclear. Moreover, the presence of catalytically inactive amylases that show starch excess phenotypes when deleted presents questions on how starch degradation is regulated. Plants lacking one of these catalytically inactive β-amylases, BAM9, have enhanced starch accumulation when combined with mutations in BAM1 and BAM3, the primary starch degrading BAMs in response to stress and at night, respectively. BAM9 has been reported to be transcriptionally induced by stress although the mechanism for BAM9 function is unclear. From yeast two-hybrid experiments, we identified the plastid-localized AMY3 as a potential interaction partner for BAM9. We found that BAM9 interacted with AMY3 in vitro and that BAM9 enhances AMY3 activity about three-fold. Modeling of the AMY3-BAM9 complex predicted a previously undescribed alpha-alpha hairpin in AMY3 that could serve as a potential interaction site. Additionally, AMY3 lacking the alpha-alpha hairpin is unaffected by BAM9. Structural analysis of AMY3 showed that it can form a homodimer in solution and that BAM9 appears to replace one of the AMY3 monomers to form a heterodimer. The presence of both BAM9 and AMY3 in many vascular plant lineages, along with model-based evidence that they heterodimerize, suggests that the interaction is conserved. Collectively these data suggest that BAM9 is a pseudoamylase that activates AMY3 in response to cellular stress, possibly facilitating stress recovery.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025913","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, 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 : 2025-01-22 DOI: 10.1002/prot.26800

Nakia Polidori, Peter Babin, Bastian Daniel, Karl Gruber

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 : 2025-01-22 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":"https://doi.org/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":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","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

AlphaFold and Docking Approaches for Antibody-Antigen and Other Targets: Insights From CAPRI Rounds 47-55. AlphaFold和抗体-抗原和其他靶点的对接方法：CAPRI第47-55轮的见解

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-01-20 DOI: 10.1002/prot.26801

Ragul Gowthaman, Minjae Park, Rui Yin, Johnathan D Guest, Brian G Pierce

{"title":"AlphaFold and Docking Approaches for Antibody-Antigen and Other Targets: Insights From CAPRI Rounds 47-55.","authors":"Ragul Gowthaman, Minjae Park, Rui Yin, Johnathan D Guest, Brian G Pierce","doi":"10.1002/prot.26801","DOIUrl":"https://doi.org/10.1002/prot.26801","url":null,"abstract":"Accurate modeling of the structures of protein-protein complexes and other biomolecular interactions represents a longstanding and important challenge for computational biology. The Critical Assessment of PRedicted Interactions (CAPRI) experiment has served for over two decades as a key means to assess and compare current approaches and methods through blind predictive scenarios, highlighting useful strategies, and new developments. Here we describe the performance of our laboratory's team in recent CAPRI rounds, which included submissions for 10 modeling targets. Our team utilized a range of docking and modeling approaches, including ZDOCK, Rosetta, and ZRANK, to model, refine, and score protein-protein and protein-DNA complexes. For recent targets we utilized adaptations of AlphaFold to generate models, leading to near-native models for an antibody-peptide target, and a highly accurate (but low ranked) model for an antibody-MHC complex. These results underscore the utility of AlphaFold-based protocols for predictive protein complex modeling, including for immune recognition, and highlight considerations regarding the use of AlphaFold confidence metrics in model selection.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017072","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 : 2025-01-18 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":"https://doi.org/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":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-18","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

High-Throughput Evaluation of Natural Diversity of F-Type ATP Synthase Rotor Ring Stoichiometries. f型ATP合成酶旋翼环化学计量学自然多样性的高通量评价。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-01-15 DOI: 10.1002/prot.26790

Stepan D Osipov, Egor V Zinovev, Arina A Anuchina, Alexander S Kuzmin, Andronika V Minaeva, Yury L Ryzhykau, Alexey V Vlasov, Ivan Yu Gushchin

{"title":"High-Throughput Evaluation of Natural Diversity of F-Type ATP Synthase Rotor Ring Stoichiometries.","authors":"Stepan D Osipov, Egor V Zinovev, Arina A Anuchina, Alexander S Kuzmin, Andronika V Minaeva, Yury L Ryzhykau, Alexey V Vlasov, Ivan Yu Gushchin","doi":"10.1002/prot.26790","DOIUrl":"https://doi.org/10.1002/prot.26790","url":null,"abstract":"Adenosine triphosphate (ATP) synthases are large enzymes present in every living cell. They consist of a transmembrane and a soluble domain, each comprising multiple subunits. The transmembrane part contains an oligomeric rotor ring (c-ring), whose stoichiometry defines the ratio between the number of synthesized ATP molecules and the number of ions transported through the membrane. Currently, c-rings of F-Type ATP synthases consisting of 8-17 (except 16) subunits have been experimentally demonstrated, but it is not known whether other stoichiometries are present in natural organisms. Here, we present an easy-to-use high-throughput computational approach based on AlphaFold that allows us to estimate the stoichiometry of all homo-oligomeric c-rings, whose sequences are present in genomic databases. We validate the approach on the available experimental data, obtaining the correlation as high as 0.94 for the reference dataset and use it to predict the existence of c-rings with stoichiometry varying at least from 8 to 27. We then conduct molecular dynamics simulations of two c-rings with stoichiometry above 17 to corroborate the machine learning-based predictions. Our work strongly suggests existence of rotor rings with previously undescribed high stoichiometry in natural organisms and highlights the utility of AlphaFold-based approaches for studying homo-oligomeric proteins.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985758","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

Sucrose and Gibberellic Acid Binding Stabilize the Inward-Open Conformation of AtSWEET13: A Molecular Dynamics Study. 蔗糖和赤霉素酸结合稳定AtSWEET13内向开放构象：分子动力学研究。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-01-15 DOI: 10.1002/prot.26799

Zoltan Palmai

{"title":"Sucrose and Gibberellic Acid Binding Stabilize the Inward-Open Conformation of AtSWEET13: A Molecular Dynamics Study.","authors":"Zoltan Palmai","doi":"10.1002/prot.26799","DOIUrl":"https://doi.org/10.1002/prot.26799","url":null,"abstract":"In plants, sugar will eventually be exported transporters (SWEETs) facilitate the translocation of mono- and disaccharides across membranes and play a critical role in modulating responses to gibberellin (GA3), a key growth hormone. However, the dynamic mechanisms underlying sucrose and GA3 binding and transport remain elusive. Here, we employed microsecond-scale molecular dynamics (MD) simulations to investigate the influence of sucrose and GA3 binding on SWEET13 transporter motions. While sucrose exhibits high flexibility within the binding pocket, GA3 remains firmly anchored in the central cavity. Binding of both ligands increases the average channel radius along the transporter's principal axis. In contrast to the apo form, which retains its initial conformation throughout the simulation, ligand-bound complexes undergo a significant conformational transition characterized by further opening of the intracellular gate relative to the inward-open crystal structure (5XPD). This opening is driven by ligand-induced bending of helix V, stabilizing the inward-open state. Sucrose binding notably enhances the flexibility of the intracellular gate and amplifies anticorrelated motions between the N- and C-terminal domains at the intracellular side, suggesting an opening-closing motion of these domains. Principal component analysis revealed that this gating motion is most pronounced in the sucrose complex and minimal in the apo form, highlighting sucrose's ability to induce high-amplitude gating. Our binding free energy calculations indicate that SWEET13 has lower binding affinity for sucrose compared to GA3, consistent with its role in sugar transport. These results provide insight into key residues involved in sucrose and GA3 binding and transport, advancing our understanding of SWEET13 dynamics.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017148","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

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 : 2025-01-09 DOI: 10.1002/prot.26796

Anuradha Singh, Naga Rajiv Lakkaniga

引用次数: 0

Decoding the Torsional Dynamics of Main-Chain Atoms Within CαNN Motif Facilitating Specific Anion Recognition. 解码c - α nn基序中主链原子的扭转动力学，促进特定阴离子识别。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-01-07 DOI: 10.1002/prot.26798

Akash Roy, Vinith Johnson, Pramiti Das, Shuvam Paul, Subhankar Sahu, Raja Banerjee

{"title":"Decoding the Torsional Dynamics of Main-Chain Atoms Within CαNN Motif Facilitating Specific Anion Recognition.","authors":"Akash Roy, Vinith Johnson, Pramiti Das, Shuvam Paul, Subhankar Sahu, Raja Banerjee","doi":"10.1002/prot.26798","DOIUrl":"https://doi.org/10.1002/prot.26798","url":null,"abstract":"The structural plasticity of proteins at the molecular level is largely dictated by backbone torsion angles, which play a critical role in ligand recognition and binding. To establish the anion-induced cooperative arrangement of the main-chain (mc) torsion, herein, we analyzed a set of naturally occurring CαNN motifs as \"static models\" for their anion-binding competence through docking and molecular dynamics simulations and decoded its torsion angle influenced mc-driven anion recognition potential. By comparing a pool of 20 distinct sets of CαNN motif with identical sequences in their \"anion bound/present, aP\" and \"anion free/absent, aA\" versions, we could discern that there exists a positive correlation between the \"difference of anion residence time (ΔRT)\" and \"difference among the main-chain torsion angle\" of the aP and aA population. Notably, the anion interaction with CαNNs is locally energetically favorable even in a context-free non-proteinaceous environment and if the difference of the mc-torsion angles involving the Cα-1, N0, N1 residues for a population is higher between the aP and aA state, the difference among the ligand RT is also greater. At the atomistic level, the accommodation of anion is highly synergistic and cooperatively sways the interacting mc-atom torsions. By comparing the clustering of H-bonding patterns, the free energy of binding, and RT in both states, we provide evidence that to establish favorable thermodynamics and kinetics of ligand accommodation in these short structural motifs, proper reorientation of local-mc governed by torsions is a prerequisite. Our findings position the CαNN motif as a promising scaffold for peptidomimetic design and emphasize the critical role of loop region dynamics in protein structure-function relationships.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959665","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