Critical assessment of protein intrinsic disorder prediction.
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ABSTRACT:
SUBMITTER: Necci M
PROVIDER: S-EPMC8105172 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDue to the functional importance of intrinsically disordered proteins or protein regions, prediction of intrinsic protein disorder from amino acid sequence has become an area of active research as witnessed in the 6th experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP6). Since the initial work by Romero et al. (Identifying disordered regions in proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997), our group has developed several predictors optimized for long disordered regions (>30 residues) with prediction accuracy exceeding 85%. However, these predictors are less successful on short disordered regions (< or =30 residues). A probable cause is a length-dependent amino acid compositions and sequence properties of disordered regions.ResultsWe proposed two new predictor models, VSL2-M1 and VSL2-M2, to address this length-dependency problem in prediction of intrinsic protein disorder. These two predictors are similar to the original VSL1 predictor used in the CASP6 experiment. In both models, two specialized predictors were first built and optimized for short (< or = 30 residues) and long disordered regions (>30 residues), respectively. A meta predictor was then trained to integrate the specialized predictors into the final predictor model. As the 10-fold cross-validation results showed, the VSL2 predictors achieved well-balanced prediction accuracies of 81% on both short and long disordered regions. Comparisons over the VSL2 training dataset via 10-fold cross-validation and a blind-test set of unrelated recent PDB chains indicated that VSL2 predictors were significantly more accurate than several existing predictors of intrinsic protein disorder.ConclusionThe VSL2 predictors are applicable to disordered regions of any length and can accurately identify the short disordered regions that are often misclassified by our previous disorder predictors. The success of the VSL2 predictors further confirmed the previously observed differences in amino acid compositions and sequence properties between short and long disordered regions, and justified our approaches for modelling short and long disordered regions separately. The VSL2 predictors are freely accessible for non-commercial use at http://www.ist.temple.edu/disprot/predictorVSL2.php.
| S-EPMC1479845 | biostudies-literature
Project description:Abstract Intrinsically disordered proteins (IDPs) are important for a broad range of biological functions and are involved in many diseases. An understanding of intrinsic disorder is key to develop compounds that target IDPs. Experimental characterization of IDPs is hindered by the very fact that they are highly dynamic. Computational methods that predict disorder from the amino acid sequence have been proposed. Here, we present ADOPT (Attention DisOrder PredicTor), a new predictor of protein disorder. ADOPT is composed of a self-supervised encoder and a supervised disorder predictor. The former is based on a deep bidirectional transformer, which extracts dense residue-level representations from Facebook’s Evolutionary Scale Modeling library. The latter uses a database of nuclear magnetic resonance chemical shifts, constructed to ensure balanced amounts of disordered and ordered residues, as a training and a test dataset for protein disorder. ADOPT predicts whether a protein or a specific region is disordered with better performance than the best existing predictors and faster than most other proposed methods (a few seconds per sequence). We identify the features that are relevant for the prediction performance and show that good performance can already be gained with <100 features. ADOPT is available as a stand-alone package at https://github.com/PeptoneLtd/ADOPT and as a web server at https://adopt.peptone.io/.
| S-EPMC10150328 | biostudies-literature
Project description:Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002-4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization enables quick identification of viruses with similar behaviors in transmission, regardless of genetic proximity. Based on this analysis, an empirical model for predicting the viral transmission behavior is developed. This model is able to explain some behavioral aspects of important coronaviruses that previously were not fully understood. The new predictor can be a useful tool for better epidemiological, clinical, and structural understanding of behavior of both newly emerging viruses and viruses that have been known for a long time. A potentially new vaccine strategy could involve searches for viral strains that are characterized by the evolutionary misfit between the peculiarities of the disorder distribution in their shells and their behavior.
| S-EPMC3477565 | biostudies-literature
Project description:Intrinsically disordered or unstructured proteins (or regions in proteins) have been found to be important in a wide range of biological functions and implicated in many diseases. Due to the high cost and low efficiency of experimental determination of intrinsic disorder and the exponential increase of unannotated protein sequences, developing complementary computational prediction methods has been an active area of research for several decades. Here, we employed an ensemble of deep Squeeze-and-Excitation residual inception and long short-term memory (LSTM) networks for predicting protein intrinsic disorder with input from evolutionary information and predicted one-dimensional structural properties. The method, called SPOT-Disorder2, offers substantial and consistent improvement not only over our previous technique based on LSTM networks alone, but also over other state-of-the-art techniques in three independent tests with different ratios of disordered to ordered amino acid residues, and for sequences with either rich or limited evolutionary information. More importantly, semi-disordered regions predicted in SPOT-Disorder2 are more accurate in identifying molecular recognition features (MoRFs) than methods directly designed for MoRFs prediction. SPOT-Disorder2 is available as a web server and as a standalone program at https://sparks-lab.org/server/spot-disorder2/.
| S-EPMC7212484 | biostudies-literature
Project description:The IntFOLD server is a novel independent server that integrates several cutting edge methods for the prediction of structure and function from sequence. Our guiding principles behind the server development were as follows: (i) to provide a simple unified resource that makes our prediction software accessible to all and (ii) to produce integrated output for predictions that can be easily interpreted. The output for predictions is presented as a simple table that summarizes all results graphically via plots and annotated 3D models. The raw machine readable data files for each set of predictions are also provided for developers, which comply with the Critical Assessment of Methods for Protein Structure Prediction (CASP) data standards. The server comprises an integrated suite of five novel methods: nFOLD4, for tertiary structure prediction; ModFOLD 3.0, for model quality assessment; DISOclust 2.0, for disorder prediction; DomFOLD 2.0 for domain prediction; and FunFOLD 1.0, for ligand binding site prediction. Predictions from the IntFOLD server were found to be competitive in several categories in the recent CASP9 experiment. The IntFOLD server is available at the following web site: http://www.reading.ac.uk/bioinf/IntFOLD/.
| S-EPMC3125722 | biostudies-literature
Project description:Intrinsically disordered regions in proteins possess important biological roles including transcriptional regulation, molecular recognition, and provision of sites for posttranslational modification. In three-dimensional crystallization of both soluble and membrane proteins, identification and removal of disordered regions is often necessary for obtaining crystals possessing sufficient long-range order for structure determination. Disordered regions can be identified experimentally, with techniques such as limited proteolysis coupled with mass spectrometry, or computationally, by using disorder prediction programs, of which many are available. Although these programs use various methods to predict disorder from a protein's primary sequence, they all were developed using information derived from soluble protein structures. Therefore, their performance and accuracy when applied to integral membrane proteins remained an open question. We evaluated the performance of 13 disorder prediction programs on a dataset containing 343 membrane proteins, and upon subdatasets containing only α-helical or β-barrel proteins. These programs were ranked using multiple metrics, including metrics specifically created for membrane proteins. Analysis of these data shows a clear distinction between programs that accurately predict disordered regions in membrane proteins and programs which perform poorly, and allows for the robust integration of in silico disorder prediction into our PSI:Biology membrane protein structural genomics pipeline.
| S-EPMC4008797 | biostudies-literature
Project description:Asparagine residues in proteins undergo spontaneous deamidation, a post-translational modification that may act as a molecular clock for the regulation of protein function and turnover. Asparagine deamidation is modulated by protein local sequence, secondary structure and hydrogen bonding. We present NGOME, an algorithm able to predict non-enzymatic deamidation of internal asparagine residues in proteins in the absence of structural data, using sequence-based predictions of secondary structure and intrinsic disorder. Compared to previous algorithms, NGOME does not require three-dimensional structures yet yields better predictions than available sequence-only methods. Four case studies of specific proteins show how NGOME may help the user identify deamidation-prone asparagine residues, often related to protein gain of function, protein degradation or protein misfolding in pathological processes. A fifth case study applies NGOME at a proteomic scale and unveils a correlation between asparagine deamidation and protein degradation in yeast. NGOME is freely available as a webserver at the National EMBnet node Argentina, URL: http://www.embnet.qb.fcen.uba.ar/ in the subpage "Protein and nucleic acid structure and sequence analysis".
| S-EPMC4682632 | biostudies-literature
Project description:CASP (critical assessment of structure prediction) assesses the state of the art in modeling protein structure from amino acid sequence. The most recent experiment (CASP13 held in 2018) saw dramatic progress in structure modeling without use of structural templates (historically "ab initio" modeling). Progress was driven by the successful application of deep learning techniques to predict inter-residue distances. In turn, these results drove dramatic improvements in three-dimensional structure accuracy: With the proviso that there are an adequate number of sequences known for the protein family, the new methods essentially solve the long-standing problem of predicting the fold topology of monomeric proteins. Further, the number of sequences required in the alignment has fallen substantially. There is also substantial improvement in the accuracy of template-based models. Other areas-model refinement, accuracy estimation, and the structure of protein assemblies-have again yielded interesting results. CASP13 placed increased emphasis on the use of sparse data together with modeling and chemical crosslinking, SAXS, and NMR all yielded more mature results. This paper summarizes the key outcomes of CASP13. The special issue of PROTEINS contains papers describing the CASP13 assessments in each modeling category and contributions from the participants.
| S-EPMC6927249 | biostudies-literature
Project description:This article reports the outcome of the 12th round of Critical Assessment of Structure Prediction (CASP12), held in 2016. CASP is a community experiment to determine the state of the art in modeling protein structure from amino acid sequence. Participants are provided sequence information and in turn provide protein structure models and related information. Analysis of the submitted structures by independent assessors provides a comprehensive picture of the capabilities of current methods, and allows progress to be identified. This was again an exciting round of CASP, with significant advances in 4 areas: (i) The use of new methods for predicting three-dimensional contacts led to a two-fold improvement in contact accuracy. (ii) As a consequence, model accuracy for proteins where no template was available improved dramatically. (iii) Models based on a structural template showed overall improvement in accuracy. (iv) Methods for estimating the accuracy of a model continued to improve. CASP continued to develop new areas: (i) Assessing methods for building quaternary structure models, including an expansion of the collaboration between CASP and CAPRI. (ii) Modeling with the aid of experimental data was extended to include SAXS data, as well as again using chemical cross-linking information. (iii) A team of assessors evaluated the suitability of models for a range of applications, including mutation interpretation, analysis of ligand binding properties, and identification of interfaces. This article describes the experiment and summarizes the results. The rest of this special issue of PROTEINS contains papers describing CASP12 results and assessments in more detail.
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Project description:Critical assessment of structure prediction (CASP) is a community experiment to advance methods of computing three-dimensional protein structure from amino acid sequence. Core components are rigorous blind testing of methods and evaluation of the results by independent assessors. In the most recent experiment (CASP14), deep-learning methods from one research group consistently delivered computed structures rivaling the corresponding experimental ones in accuracy. In this sense, the results represent a solution to the classical protein-folding problem, at least for single proteins. The models have already been shown to be capable of providing solutions for problematic crystal structures, and there are broad implications for the rest of structural biology. Other research groups also substantially improved performance. Here, we describe these results and outline some of the many implications. Other related areas of CASP, including modeling of protein complexes, structure refinement, estimation of model accuracy, and prediction of inter-residue contacts and distances, are also described.
| S-EPMC8726744 | biostudies-literature