Dataset Information

Multi-criteria protein structure comparison and structural similarities analysis using pyMCPSC.

ABSTRACT: Protein Structure Comparison (PSC) is a well developed field of computational proteomics with active interest from the research community, since it is widely used in structural biology and drug discovery. With new PSC methods continuously emerging and no clear method of choice, Multi-Criteria Protein Structure Comparison (MCPSC) is commonly employed to combine methods and generate consensus structural similarity scores. We present pyMCPSC, a Python based utility we developed to allow users to perform MCPSC efficiently, by exploiting the parallelism afforded by the multi-core CPUs of today's desktop computers. We show how pyMCPSC facilitates the analysis of similarities in protein domain datasets and how it can be extended to incorporate new PSC methods as they are becoming available. We exemplify the power of pyMCPSC using a case study based on the Proteus_300 dataset. Results generated using pyMCPSC show that MCPSC scores form a reliable basis for identifying the true classification of a domain, as evidenced both by the ROC analysis as well as the Nearest-Neighbor analysis. Structure similarity based "Phylogenetic Trees" representation generated by pyMCPSC provide insight into functional grouping within the dataset of domains. Furthermore, scatter plots generated by pyMCPSC show the existence of strong correlation between protein domains belonging to SCOP Class C and loose correlation between those of SCOP Class D. Such analyses and corresponding visualizations help users quickly gain insights about their datasets. The source code of pyMCPSC is available under the GPLv3.0 license through a GitHub repository (https://github.com/xulesc/pymcpsc).

SUBMITTER: Sharma A

PROVIDER: S-EPMC6192565 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Multi-criteria protein structure comparison and structural similarities analysis using pyMCPSC.

Sharma Anuj A Manolakos Elias S ES

PloS one 20181017 10

Protein Structure Comparison (PSC) is a well developed field of computational proteomics with active interest from the research community, since it is widely used in structural biology and drug discovery. With new PSC methods continuously emerging and no clear method of choice, Multi-Criteria Protein Structure Comparison (MCPSC) is commonly employed to combine methods and generate consensus structural similarity scores. We present pyMCPSC, a Python based utility we developed to allow users to pe ...[more]

PMID: 30332415

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Project description:BACKGROUND:Protein structure comparison play important role in in silico functional prediction of a new protein. It is also used for understanding the evolutionary relationships among proteins. A variety of methods have been proposed in literature for comparing protein structures but they have their own limitations in terms of accuracy and complexity with respect to computational time and space. There is a need to improve the computational complexity in comparison/alignment of proteins through incorporation of important biological and structural properties in the existing techniques. RESULTS:An efficient algorithm has been developed for comparing protein structures using elastic shape analysis in which the sequence of 3D coordinates atoms of protein structures supplemented by additional auxiliary information from side-chain properties are incorporated. The protein structure is represented by a special function called square-root velocity function. Furthermore, singular value decomposition and dynamic programming have been employed for optimal rotation and optimal matching of the proteins, respectively. Also, geodesic distance has been calculated and used as the dissimilarity score between two protein structures. The performance of the developed algorithm is tested and found to be more efficient, i.e., running time reduced by 80-90 % without compromising accuracy of comparison when compared with the existing methods. Source codes for different functions have been developed in R. Also, user friendly web-based application called ProtSComp has been developed using above algorithm for comparing protein 3D structures and is accessible free. CONCLUSIONS:The methodology and algorithm developed in this study is taking considerably less computational time without loss of accuracy (Table 2). The proposed algorithm is considering different criteria of representing protein structures using 3D coordinates of atoms and inclusion of residue wise molecular properties as auxiliary information.

Project description:One approach for speeding-up protein structure comparison is the projection approach, where a protein structure is mapped to a high-dimensional vector and structural similarity is approximated by distance between the corresponding vectors. Structural footprinting methods are projection methods that employ the same general technique to produce the mapping: first select a representative set of structural fragments as models and then map a protein structure to a vector in which each dimension corresponds to a particular model and "counts" the number of times the model appears in the structure. The main difference between any two structural footprinting methods is in the set of models they use; in fact a large number of methods can be generated by varying the type of structural fragments used and the amount of detail in their representation. How do these choices affect the ability of the method to detect various types of structural similarity?To answer this question we benchmarked three structural footprinting methods that vary significantly in their selection of models against the CATH database. In the first set of experiments we compared the methods' ability to detect structural similarity characteristic of evolutionarily related structures, i.e., structures within the same CATH superfamily. In the second set of experiments we tested the methods' agreement with the boundaries imposed by classification groups at the Class, Architecture, and Fold levels of the CATH hierarchy.In both experiments we found that the method which uses secondary structure information has the best performance on average, but no one method performs consistently the best across all groups at a given classification level. We also found that combining the methods' outputs significantly improves the performance. Moreover, our new techniques to measure and visualize the methods' agreement with the CATH hierarchy, including the threshholded affinity graph, are useful beyond this work. In particular, they can be used to expose a similar composition of different classification groups in terms of structural fragments used by the method and thus provide an alternative demonstration of the continuous nature of the protein structure universe.

Project description:BackgroundA recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2) database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR) protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function.FindingsWe report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG) to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated.ConclusionsCPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores for false positives by ~30%, while leaving true positives unaffected. Importantly, receiver operating characteristics (ROC) curves demonstrate the high correlation between CPASS similarity scores and an accurate functional assignment. As indicated by distribution curves, scores ≥ 30% infer a functional similarity. Software URL: http://cpass.unl.edu.

Dataset Information

Multi-criteria protein structure comparison and structural similarities analysis using pyMCPSC.

Publications

Multi-criteria protein structure comparison and structural similarities analysis using pyMCPSC.

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