CrystalCMP: automatic comparison of molecular structures.
Ontology highlight
ABSTRACT:
SUBMITTER: Rohlicek J
PROVIDER: S-EPMC7312150 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A description of REMO22, a new molecular replacement program for proteins and nucleic acids, is provided. This program, as with REMO09, can use various types of prior information through appropriate conditional distribution functions. Its efficacy in model searching has been validated through several test cases involving proteins and nucleic acids. Although REMO22 can be configured with different protocols according to user directives, it has been developed primarily as an automated tool for determining the crystal structures of macromolecules. To evaluate REMO22's utility in the current crystallographic environment, its experimental results must be compared favorably with those of the most widely used Molecular Replacement (MR) programs. To accomplish this, we chose two leading tools in the field, PHASER and MOLREP. REMO22, along with MOLREP and PHASER, were included in pipelines that contain two additional steps: phase refinement (SYNERGY) and automated model building (CAB). To evaluate the effectiveness of REMO22, SYNERGY and CAB, we conducted experimental tests on numerous macromolecular structures. The results indicate that REMO22, along with its pipeline REMO22 + SYNERGY + CAB, presents a viable alternative to currently used phasing tools.
| S-EPMC10094557 | biostudies-literature
Project description:Background and purposeWe developed an automatic method to segment cardiac substructures given a radiotherapy planning CT images to support epidemiological studies or clinical trials looking at cardiac disease endpoints after radiotherapy.Material and methodsWe used a most-similar atlas selection algorithm and 3D deformation combined with 30 detailed cardiac atlases. We cross-validated our method within the atlas library by evaluating geometric comparison metrics and by comparing cardiac doses for simulated breast radiotherapy between manual and automatic contours. We analyzed the impact of the number of cardiac atlas in the library and the use of manual guide points on the performance of our method.ResultsThe Dice Similarity Coefficients from the cross-validation reached up to 97% (whole heart) and 80% (chambers). The Average Surface Distance for the coronary arteries was less than 10.3 mm on average, with the best agreement (7.3 mm) in the left anterior descending artery (LAD). The dose comparison for simulated breast radiotherapy showed differences less than 0.06 Gy for the whole heart and atria, and 0.3 Gy for the ventricles. For the coronary arteries, the dose differences were 2.3 Gy (LAD) and 0.3 Gy (other arteries). The sensitivity analysis showed no notable improvement beyond ten atlases and the manual guide points does not significantly improve performance.ConclusionWe developed an automated method to contour cardiac substructures for radiotherapy CTs. When combined with accurate dose calculation techniques, our method should be useful for cardiac dose reconstruction of a large number of patients in epidemiological studies or clinical trials.
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Project description:Molecular fragmentation is an effective suite of approaches to reduce the formal computational complexity of quantum chemistry calculations while enhancing their algorithmic parallelisability. However, the practical applicability of fragmentation techniques remains hindered by a dearth of automation and effective metrics to assess the quality of a fragmentation scheme. In this article, we present the Quick Fragmentation via Automated Genetic Search (QFRAGS), a novel automated fragmentation algorithm that uses a genetic optimisation procedure to generate molecular fragments that yield low energy errors when adopted in Many Body Expansions (MBEs). Benchmark testing of QFRAGS on protein systems with less than 500 atoms, using two-body (MBE2) and three-body (MBE3) MBE calculations at the HF/6-31G* level, reveals mean absolute energy errors (MAEE) of 20.6 and 2.2 kJ mol-1 , respectively. For larger protein systems exceeding 500 atoms, MAEEs are 181.5 kJ mol-1 for MBE2 and 24.3 kJ mol-1 for MBE3. Furthermore, when compared to three manual fragmentation schemes on a 40-protein dataset, using both MBE and Fragment Molecular Orbital techniques, QFRAGS achieves comparable or often lower MAEEs. When applied to a 10-lipoglycan/glycolipid dataset, MAEs of 7.9 and 0.3 kJ mol-1 were observed at the MBE2 and MBE3 levels, respectively.Scientific Contribution This Article presents the Quick Fragmentation via Automated Genetic Search (QFRAGS), an innovative molecular fragmentation algorithm that significantly improves upon existing molecular fragmentation approaches by specifically addressing their lack of automation and effective fragmentation quality metrics. With an evolutionary optimisation strategy, QFRAGS actively pursues high quality fragments, generating fragmentation schemes that exhibit minimal energy errors on systems with hundreds to thousands of atoms. The advent of QFRAGS represents a significant advancement in molecular fragmentation, greatly improving the accessibility and computational feasibility of accurate quantum chemistry calculations.
| S-EPMC11331744 | biostudies-literature
Project description:Processes in organisations, such as hospitals, may deviate from the intended standard processes, due to unforeseeable events and the complexity of the organisation. For hospitals, the knowledge of actual patient streams for patient populations (e.g., severe or non-severe cases) is important for quality control and improvement. Process discovery from event data in electronic health records can shed light on the patient flows, but their comparison for different populations is cumbersome and time-consuming. In this paper, we present an approach for the automatic comparison of process models that were extracted from events in electronic health records. Concretely, we propose comparing processes for different patient populations by cross-log conformance checking, and standard graph similarity measures obtained from the directed graph underlying the process model. We perform a user study with 20 participants in order to obtain a ground truth for similarity of process models. We evaluate our approach on two data sets, the publicly available MIMIC database with the focus on different cancer patients in intensive care, and a database on breast cancer patients from a Dutch hospital. In our experiments, we found average fitness to be a good indicator for visual similarity in the ZGT use case, while the average precision and graph edit distance are strongly correlated with visual impression for cancer process models on MIMIC. These results are a call for further research and evaluation for determining which similarity or combination of similarities is needed in which type of process model comparison.
| S-EPMC7460145 | biostudies-literature
Project description:The amount of data from languages spoken all over the world is rapidly increasing. Traditional manual methods in historical linguistics need to face the challenges brought by this influx of data. Automatic approaches to word comparison could provide invaluable help to pre-analyze data which can be later enhanced by experts. In this way, computational approaches can take care of the repetitive and schematic tasks leaving experts to concentrate on answering interesting questions. Here we test the potential of automatic methods to detect etymologically related words (cognates) in cross-linguistic data. Using a newly compiled database of expert cognate judgments across five different language families, we compare how well different automatic approaches distinguish related from unrelated words. Our results show that automatic methods can identify cognates with a very high degree of accuracy, reaching 89% for the best-performing method Infomap. We identify the specific strengths and weaknesses of these different methods and point to major challenges for future approaches. Current automatic approaches for cognate detection-although not perfect-could become an important component of future research in historical linguistics.
| S-EPMC5271327 | biostudies-literature
Project description:Macromolecular crystal structures in the Protein Data Bank (PDB) are a key source of structural insight into biological processes. These structures, some >30 years old, were constructed with methods of their era. With PDB_REDO, we aim to automatically optimize these structures to better fit their corresponding experimental data, passing the benefits of new methods in crystallography on to a wide base of non-crystallographer structure users.We developed new algorithms to allow automatic rebuilding and remodeling of main chain peptide bonds and side chains in crystallographic electron density maps, and incorporated these and further enhancements in the PDB_REDO procedure. Applying the updated PDB_REDO to the oldest, but also to some of the newest models in the PDB, corrects existing modeling errors and brings these models to a higher quality, as judged by standard validation methods.The PDB_REDO database and links to all software are available at http://www.cmbi.ru.nl/pdb_redo.r.joosten@nki.nl; a.perrakis@nki.nlSupplementary data are available at Bioinformatics online.
| S-EPMC3232375 | biostudies-literature
Project description:Homology modeling predicts the 3D structure of a query protein based on the sequence alignment with one or more template proteins of known structure. Its great importance for biological research is owed to its speed, simplicity, reliability and wide applicability, covering more than half of the residues in protein sequence space. Although multiple templates have been shown to generally increase model quality over single templates, the information from multiple templates has so far been combined using empirically motivated, heuristic approaches. We present here a rigorous statistical framework for multi-template homology modeling. First, we find that the query proteins' atomic distance restraints can be accurately described by two-component Gaussian mixtures. This insight allowed us to apply the standard laws of probability theory to combine restraints from multiple templates. Second, we derive theoretically optimal weights to correct for the redundancy among related templates. Third, a heuristic template selection strategy is proposed. We improve the average GDT-ha model quality score by 11% over single template modeling and by 6.5% over a conventional multi-template approach on a set of 1000 query proteins. Robustness with respect to wrong constraints is likewise improved. We have integrated our multi-template modeling approach with the popular MODELLER homology modeling software in our free HHpred server http://toolkit.tuebingen.mpg.de/hhpred and also offer open source software for running MODELLER with the new restraints at https://bitbucket.org/soedinglab/hh-suite.
| S-EPMC4619893 | biostudies-literature
Project description:Improvements in crystallographic hardware and software have allowed automated structure-solution pipelines to approach a near-`one-click' experience for the initial determination of macromolecular structures. However, in many cases the resulting initial model requires a laborious, iterative process of refinement and validation. A new method has been developed for the automatic modeling of side-chain conformations that takes advantage of rotamer-prediction methods in a crystallographic context. The algorithm, which is based on deterministic dead-end elimination (DEE) theory, uses new dense conformer libraries and a hybrid energy function derived from experimental data and prior information about rotamer frequencies to find the optimal conformation of each side chain. In contrast to existing methods, which incorporate the electron-density term into protein-modeling frameworks, the proposed algorithm is designed to take advantage of the highly discriminatory nature of electron-density maps. This method has been implemented in the program Fitmunk, which uses extensive conformational sampling. This improves the accuracy of the modeling and makes it a versatile tool for crystallographic model building, refinement and validation. Fitmunk was extensively tested on over 115 new structures, as well as a subset of 1100 structures from the PDB. It is demonstrated that the ability of Fitmunk to model more than 95% of side chains accurately is beneficial for improving the quality of crystallographic protein models, especially at medium and low resolutions. Fitmunk can be used for model validation of existing structures and as a tool to assess whether side chains are modeled optimally or could be better fitted into electron density. Fitmunk is available as a web service at http://kniahini.med.virginia.edu/fitmunk/server/ or at http://fitmunk.bitbucket.org/.
| S-EPMC4756610 | biostudies-literature
Project description:MotivationComplementing structural information with biochemical and biomedical annotations is a powerful approach to explore the biological function of macromolecular complexes. However, currently the compilation of annotations and structural data is a feature only available for those structures that have been released as entries to the Protein Data Bank.ResultsTo help researchers in assessing the consistency between structures and biological annotations for structural models not deposited in databases, we present 3DBIONOTES v2.0, a web application designed for the automatic annotation of biochemical and biomedical information onto macromolecular structural models determined by any experimental or computational technique.Availability and implementationThe web server is available at http://3dbionotes-ws.cnb.csic.es.Contactjsegura@cnb.csic.es.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC5870569 | biostudies-literature
Project description:BackgroundKnowledge of protein-DNA interactions at the structural-level can provide insights into the mechanisms of protein-DNA recognition and gene regulation. Although over 1400 protein-DNA complex structures have been deposited into Protein Data Bank (PDB), the structural details of protein-DNA interactions are generally not available. In addition, current approaches to comparison of protein-DNA complexes are mainly based on protein sequence similarity while the DNA sequences are not taken into account. With the number of experimentally-determined protein-DNA complex structures increasing, there is a need for an automatic program to analyze the protein-DNA complex structures and to provide comprehensive structural information for the benefit of the whole research community.ResultsWe developed an automatic and comprehensive protein-DNA complex structure analysis program, PDA (for protein-DNA complex structure analyzer). PDA takes PDB files as inputs and performs structural analysis that includes 1) whole protein-DNA complex structure restoration, especially the reconstruction of double-stranded DNA structures; 2) an efficient new approach for DNA base-pair detection; 3) systematic annotation of protein-DNA interactions; and 4) extraction of DNA subsequences involved in protein-DNA interactions and identification of protein-DNA binding units. Protein-DNA complex structures in current PDB were processed and analyzed with our PDA program and the analysis results were stored in a database. A dataset useful for studying protein-DNA interactions involved in gene regulation was generated using both protein and DNA sequences as well as the contact information of the complexes. WebPDA was developed to provide a web interface for using PDA and for data retrieval.ConclusionPDA is a computational tool for structural annotations of protein-DNA complexes. It provides a useful resource for investigating protein-DNA interactions. Data from the PDA analysis can also facilitate the classification of protein-DNA complexes and provide insights into rational design of benchmarks. The PDA program is freely available at http://bioinfozen.uncc.edu/webpda.
| S-EPMC2709256 | biostudies-literature