Acta Crystallographica. Section D, Structural Biology最新文献

AlphaFold-guided molecular replacement for solving challenging crystal structures. alphafold引导分子替代解决具有挑战性的晶体结构。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2025-01-01 DOI: 10.1107/S2059798324011999

Wei Wang, Zhen Gong, Wayne A Hendrickson

{"title":"AlphaFold-guided molecular replacement for solving challenging crystal structures.","authors":"Wei Wang, Zhen Gong, Wayne A Hendrickson","doi":"10.1107/S2059798324011999","DOIUrl":"10.1107/S2059798324011999","url":null,"abstract":"Molecular replacement (MR) is highly effective for biomolecular crystal structure determination, increasingly so as the database of known structures has increased. For candidates without recognizable similarity to known structures, however, crystal structure analyses have nearly always required experiments for de novo phase evaluation. Now, with the unprecedented accuracy of AlphaFold predictions of protein structures from amino-acid sequences, an appreciable expansion of the reach of MR for proteins is realized. Here, we sought to automate an AlphaFold-guided MR procedure that tailors predictions to the MR problem at hand. We first optimized the reliability cutoff parameters for residue inclusion as tested in application to a previously MR-intractable problem. We then examined cases where AlphaFold by default predicts a conformation alternative to that of the candidate structure, devising tests for MR solution either from domain-specific predictions or from predictions based on diverse sequence subclusters. We tested subclustering procedures on an enzyme system that entails multiple MR-challenging conformations. The overall process as implemented in Phenix automatically surveys a succession of trials of increasing computational complexity until an MR solution is found or the options are exhausted. Validated MR solutions were found for 92% of one set of 158 challenging problems from the PDB and 93% of those from a second set of 215 challenges. Thus, many crystal structure analyses that previously required experimental phase evaluation can now be solved by AlphaFold-guided MR. In effect, this and related MR approaches are de novo phasing methods.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"4-21"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Making the most of an abundance of data. 充分利用丰富的数据。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2025-01-01 DOI: 10.1107/S205979832401204X

Christoph Mueller-Dieckmann, Anna J Warren, David G Waterman

引用次数: 0

Useful experimental aspects of small-wedge synchrotron crystallography for accurate structure analysis of protein molecules. 小楔同步加速器晶体学对蛋白质分子精确结构分析的有用实验方面。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2025-01-01 DOI: 10.1107/S2059798324011987

Kunio Hirata

{"title":"Useful experimental aspects of small-wedge synchrotron crystallography for accurate structure analysis of protein molecules.","authors":"Kunio Hirata","doi":"10.1107/S2059798324011987","DOIUrl":"10.1107/S2059798324011987","url":null,"abstract":"Recent advances in low-emittance synchrotron X-ray technology and highly sensitive photon-counting detectors have revolutionized protein micro-crystallography in structural biology. These developments and improvements to sample-exchange robots and beamline control have paved the way for automated and efficient unattended data collection. This study analyzed protein crystal structures such as type 2 angiotensin II receptor, CNNM/CorC membrane proteins and polyhedral protein crystals using small-wedge synchrotron crystallography (SWSX), which dramatically improves measurement efficiency through automated measurement. We evaluated the data quality using SWSX, focusing on `massive data collection'. In this context, `massive' refers to data sets with a multiplicity exceeding 100. The findings could potentially lead to the development of more efficient experimental conditions, such as obtaining high-resolution data using a smaller number of crystals. We have demonstrated that the application of machine learning, a modern key component of data science, to classify data groups is an integral part of the analysis process and may play a crucial role in improving data quality. These results indicate that SWSX is one of the essential candidates for crystal structure analysis methods for difficult-to-analyze samples: it can enable diverse and complex protein functional analysis.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"22-37"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The 1.3 Å resolution structure of the truncated group Ia type IV pilin from Pseudomonas aeruginosa strain P1. 铜绿假单胞菌P1株截短的Ia族IV型蛋白的1.3 Å分辨率结构。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-12-01 Epub Date: 2024-11-28 DOI: 10.1107/S205979832401132X

Nicholas Bragagnolo, Gerald F Audette

{"title":"The 1.3 Å resolution structure of the truncated group Ia type IV pilin from Pseudomonas aeruginosa strain P1.","authors":"Nicholas Bragagnolo, Gerald F Audette","doi":"10.1107/S205979832401132X","DOIUrl":"10.1107/S205979832401132X","url":null,"abstract":"The type IV pilus is a diverse molecular machine capable of conferring a variety of functions and is produced by a wide range of bacterial species. The ability of the pilus to perform host-cell adherence makes it a viable target for the development of vaccines against infection by human pathogens such as Pseudomonas aeruginosa. Here, the 1.3 Å resolution crystal structure of the N-terminally truncated type IV pilin from P. aeruginosa strain P1 (ΔP1) is reported, the first structure of its phylogenetically linked group (group I) to be discussed in the literature. The structure was solved from X-ray diffraction data that were collected 20 years ago with a molecular-replacement search model generated using AlphaFold; the effectiveness of other search models was analyzed. Examination of the high-resolution ΔP1 structure revealed a solvent network that aids in maintaining the fold of the protein. On comparing the sequence and structure of P1 with a variety of type IV pilins, it was observed that there are cases of higher structural similarities between the phylogenetic groups of P. aeruginosa than there are between the same phylogenetic group, indicating that a structural grouping of pilins may be necessary in developing antivirulence drugs and vaccines. These analyses also identified the α-β loop as the most structurally diverse domain of the pilins, which could allow it to serve a role in pilus recognition. Studies of ΔP1 in vitro polymerization demonstrate that the optimal hydrophobic catalyst for the oligomerization of the pilus from strain K122 is not conducive for pilus formation of ΔP1; a model of a three-start helical assembly using the ΔP1 structure indicates that the α-β loop and the D-loop prevent in vitro polymerization.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"834-849"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photosystem II: light-dependent oscillation of ligand composition at its active site. 光系统II：活性位点配体组成的光依赖性振荡。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-12-01 Epub Date: 2024-11-28 DOI: 10.1107/S2059798324011392

Jimin Wang

{"title":"Photosystem II: light-dependent oscillation of ligand composition at its active site.","authors":"Jimin Wang","doi":"10.1107/S2059798324011392","DOIUrl":"10.1107/S2059798324011392","url":null,"abstract":"Recently, the conclusions drawn from crystallographic data about the number of oxygen ligands associated with the CaMn4 cofactor in the oxygen-evolving center (OEC) of Thermosynechococcus vulcanus photosystem II (PSII) have been called into question. Here, using OEC-omit, metal ion-omit and ligand-omit electron-density maps, it is shown that the number of oxygen ligands ranges from three in the functional OEC of monomer B following dark adaption (0F), i.e. in its ground state (PDB entry 6jlj/0F and PDB entry 6jlm/0F), to five for both monomers of PSII in photo-advanced states following exposure to one and two flashes of light. For a significant fraction of the 0F OECs in monomer A, the number is four (PDB entry 6jlj/0F). Following one flash it increases to five (PDB entry 6jlk/1F), where it remains after a second flash (PDB entry 6jlj/2F). Following a third flash (3F), it decreases to three (PDB entry 6jlp/3F), suggesting that an O2 molecule has been produced. These observations suggest a mechanism for the reaction that transforms the O atoms of the water molecules bound at the O3 and O1 sites of the OEC into O2.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"850-861"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749695","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

Improving macromolecular structure refinement with metal-coordination restraints. 利用金属配位约束改善大分子结构的细化。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-12-01 Epub Date: 2024-12-03 DOI: 10.1107/S2059798324011458

Kaveh H Babai, Fei Long, Martin Malý, Keitaro Yamashita, Garib N Murshudov

{"title":"Improving macromolecular structure refinement with metal-coordination restraints.","authors":"Kaveh H Babai, Fei Long, Martin Malý, Keitaro Yamashita, Garib N Murshudov","doi":"10.1107/S2059798324011458","DOIUrl":"10.1107/S2059798324011458","url":null,"abstract":"Metals are essential components for the structure and function of many proteins. However, accurate modelling of their coordination environments remains a challenge due to the complexity and diversity of metal-coordination geometries. To address this, a method is presented for extracting and analysing coordination information, including bond lengths and angles, from the Crystallography Open Database. By using these data, comprehensive descriptions of metal-containing components are generated. A stereochemical information generator for a particular component within a specific macromolecule leverages an example PDB/mmCIF file containing the component to account for the actual surrounding environment. A matching process has been developed and implemented to align the derived metal structures with idealized coordinates from a coordination geometry library. Additionally, various strategies, depending on the quality of the matches, were employed to compile distance and angle statistics for the refinement of macromolecular structures. The developed methods were implemented in a new program, MetalCoord, that classifies and utilizes the metal-coordination geometry. The effectiveness of the developed algorithms was tested using metal-containing components from the PDB. As a result, metal-containing components from the CCP4 monomer library have been updated. The updated monomer dictionaries, in concert with the derived restraints, can be used in most structural biology computations, including macromolecular crystallography, single-particle cryo-EM and even molecular mechanics.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"821-833"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peter Main (1939-2024). 彼得·梅因（1939-2024）。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI: 10.1107/S2059798324010854

Eleanor Dodson, Kathryn Cowtan

引用次数: 0

Everyone is using biological structures, but how does one find the structure(s) one wants? 每个人都在使用生物结构，但是如何找到自己想要的结构呢？

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-12-01 Epub Date: 2024-12-05 DOI: 10.1107/S2059798324007848

Charles S Bond, Joel L Sussman

引用次数: 0

The success rate of processed predicted models in molecular replacement: implications for experimental phasing in the AlphaFold era. 分子置换中经过处理的预测模型的成功率：对 AlphaFold 时代实验分期的影响。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-11-01 Epub Date: 2024-10-03 DOI: 10.1107/S2059798324009380

Ronan M Keegan, Adam J Simpkin, Daniel J Rigden

{"title":"The success rate of processed predicted models in molecular replacement: implications for experimental phasing in the AlphaFold era.","authors":"Ronan M Keegan, Adam J Simpkin, Daniel J Rigden","doi":"10.1107/S2059798324009380","DOIUrl":"10.1107/S2059798324009380","url":null,"abstract":"The availability of highly accurate protein structure predictions from AlphaFold2 (AF2) and similar tools has hugely expanded the applicability of molecular replacement (MR) for crystal structure solution. Many structures can be solved routinely using raw models, structures processed to remove unreliable parts or models split into distinct structural units. There is therefore an open question around how many and which cases still require experimental phasing methods such as single-wavelength anomalous diffraction (SAD). Here, this question is addressed using a large set of PDB depositions that were solved by SAD. A large majority (87%) could be solved using unedited or minimally edited AF2 predictions. A further 18 (4%) yield straightforwardly to MR after splitting of the AF2 prediction using Slice'N'Dice, although different splitting methods succeeded on slightly different sets of cases. It is also found that further unique targets can be solved by alternative modelling approaches such as ESMFold (four cases), alternative MR approaches such as ARCIMBOLDO and AMPLE (two cases each), and multimeric model building with AlphaFold-Multimer or UniFold (three cases). Ultimately, only 12 cases, or 3% of the SAD-phased set, did not yield to any form of MR tested here, offering valuable hints as to the number and the characteristics of cases where experimental phasing remains essential for macromolecular structure solution.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"766-779"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Welcoming two new Co-editors. 欢迎两位新任联合编辑。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI: 10.1107/S2059798324010350

Charles S Bond, Elspeth F Garman, Randy J Read

引用次数: 0