Combining prediction of secondary structure and solvent accessibility in proteins. 2005

Rafał Adamczak, and Aleksey Porollo, and Jarosław Meller
Biomedical Informatics, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.

Owing to the use of evolutionary information and advanced machine learning protocols, secondary structures of amino acid residues in proteins can be predicted from the primary sequence with more than 75% per-residue accuracy for the 3-state (i.e., helix, beta-strand, and coil) classification problem. In this work we investigate whether further progress may be achieved by incorporating the relative solvent accessibility (RSA) of an amino acid residue as a fingerprint of the overall topology of the protein. Toward that goal, we developed a novel method for secondary structure prediction that uses predicted RSA in addition to attributes derived from evolutionary profiles. Our general approach follows the 2-stage protocol of Rost and Sander, with a number of Elman-type recurrent neural networks (NNs) combined into a consensus predictor. The RSA is predicted using our recently developed regression-based method that provides real-valued RSA, with the overall correlation coefficients between the actual and predicted RSA of about 0.66 in rigorous tests on independent control sets. Using the predicted RSA, we were able to improve the performance of our secondary structure prediction by up to 1.4% and achieved the overall per-residue accuracy between 77.0% and 78.4% for the 3-state classification problem on different control sets comprising, together, 603 proteins without homology to proteins included in the training. The effects of including solvent accessibility depend on the quality of RSA prediction. In the limit of perfect prediction (i.e., when using the actual RSA values derived from known protein structures), the accuracy of secondary structure prediction increases by up to 4%. We also observed that projecting real-valued RSA into 2 discrete classes with the commonly used threshold of 25% RSA decreases the classification accuracy for secondary structure prediction. While the level of improvement of secondary structure prediction may be different for prediction protocols that implicitly account for RSA in other ways, we conclude that an increase in the 3-state classification accuracy may be achieved when combining RSA with a state-of-the-art protocol utilizing evolutionary profiles. The new method is available through a Web server at http://sable.cchmc.org.

UI MeSH Term Description Entries
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012997 Solvents Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant & Hackh's Chemical Dictionary, 5th ed) Solvent
D015203 Reproducibility of Results The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results. Reliability and Validity,Reliability of Result,Reproducibility Of Result,Reproducibility of Finding,Validity of Result,Validity of Results,Face Validity,Reliability (Epidemiology),Reliability of Results,Reproducibility of Findings,Test-Retest Reliability,Validity (Epidemiology),Finding Reproducibilities,Finding Reproducibility,Of Result, Reproducibility,Of Results, Reproducibility,Reliabilities, Test-Retest,Reliability, Test-Retest,Result Reliabilities,Result Reliability,Result Validities,Result Validity,Result, Reproducibility Of,Results, Reproducibility Of,Test Retest Reliability,Validity and Reliability,Validity, Face
D016384 Consensus Sequence A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences. Consensus Sequences,Sequence, Consensus,Sequences, Consensus
D016571 Neural Networks, Computer A computer architecture, implementable in either hardware or software, modeled after biological neural networks. Like the biological system in which the processing capability is a result of the interconnection strengths between arrays of nonlinear processing nodes, computerized neural networks, often called perceptrons or multilayer connectionist models, consist of neuron-like units. A homogeneous group of units makes up a layer. These networks are good at pattern recognition. They are adaptive, performing tasks by example, and thus are better for decision-making than are linear learning machines or cluster analysis. They do not require explicit programming. Computational Neural Networks,Connectionist Models,Models, Neural Network,Neural Network Models,Neural Networks (Computer),Perceptrons,Computational Neural Network,Computer Neural Network,Computer Neural Networks,Connectionist Model,Model, Connectionist,Model, Neural Network,Models, Connectionist,Network Model, Neural,Network Models, Neural,Network, Computational Neural,Network, Computer Neural,Network, Neural (Computer),Networks, Computational Neural,Networks, Computer Neural,Networks, Neural (Computer),Neural Network (Computer),Neural Network Model,Neural Network, Computational,Neural Network, Computer,Neural Networks, Computational,Perceptron
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein

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