Premium
Relationship between multiple sequence alignments and quality of protein comparative models
Author(s) -
Cozzetto Domenico,
Tramontano Anna
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20284
Subject(s) - casp , a priori and a posteriori , similarity (geometry) , sequence (biology) , computer science , multiple sequence alignment , divergence (linguistics) , protein structure prediction , set (abstract data type) , protein superfamily , sequence alignment , threading (protein sequence) , quality (philosophy) , loop modeling , basis (linear algebra) , alignment free sequence analysis , algorithm , structural alignment , computational biology , protein structure , artificial intelligence , mathematics , biology , peptide sequence , genetics , biochemistry , philosophy , linguistics , geometry , epistemology , gene , image (mathematics) , programming language
Comparative modeling is the method of choice, whenever applicable, for protein structure prediction, not only because of its higher accuracy compared to alternative methods, but also because it is possible to estimate a priori the quality of the models that it can produce, thereby allowing the usefulness of a model for a given application to be assessed beforehand. By and large, the quality of a comparative model depends on two factors: the extent of structural divergence between the target and the template and the quality of the sequence alignment between the two protein sequences. The latter is usually derived from a multiple sequence alignment (MSA) of as many proteins of the family as possible, and its accuracy depends on the number and similarity distribution of the sequences of the protein family. Here we describe a method to evaluate the expected difficulty, and by extension accuracy, of a comparative model on the basis of the MSA used to build it. The parameter that we derive is used to compare the results obtained in the last two editions of the Critical Assessment of Methods for Structure Prediction (CASP) experiment as a function of the difficulty of the modeling exercise. Our analysis demonstrates that the improvement in the scope and quality of comparative models between the two experiments is largely due to the increased number of available protein sequences and to the consequent increased chance that a large and appropriately spaced set of protein sequences homologous to the proteins of interest is available. Proteins 2005. © 2004 Wiley‐Liss, Inc.