Abstract
The goal of computational protein structure prediction is to provide three-dimensional (3D) structures with resolution comparable to experimental results. Comparative modeling, which predicts the 3D structure of a protein based on its sequence similarity to homologous structures, is the most accurate computational method for structure prediction. In the last two decades, significant progress has been made on comparative modeling methods. Using the large number of protein structures deposited in the Protein Data Bank (∼65,000), automatic prediction pipelines are generating a tremendous number of models (∼1.9 million) for sequences whose structures have not been experimentally determined. Accurate models are suitable for a wide range of applications, such as prediction of protein binding sites, prediction of the effect of protein mutations, and structure-guided virtual screening. In particular, comparative modeling has enabled structure-based drug design against protein targets with unknown structures. In this review, we describe the theoretical basis of comparative modeling, the available automatic methods and databases, and the algorithms to evaluate the accuracy of predicted structures. Finally, we discuss relevant applications in the prediction of important drug target proteins, focusing on the G protein-coupled receptor (GPCR) and protein kinase families.
Keywords: Protein structure prediction, comparative modeling, sequence alignment, homology, drug target, drug design, 3D structure, Protein Data Bank, G protein-coupled receptor, protein kinase families, Comparative Modeling Method
Combinatorial Chemistry & High Throughput Screening
Title: Comparative Modeling: The State of the Art and Protein Drug Target Structure Prediction
Volume: 14 Issue: 6
Author(s): Tianyun Liu, Grace W. Tang and Emidio Capriotti
Affiliation:
Keywords: Protein structure prediction, comparative modeling, sequence alignment, homology, drug target, drug design, 3D structure, Protein Data Bank, G protein-coupled receptor, protein kinase families, Comparative Modeling Method
Abstract: The goal of computational protein structure prediction is to provide three-dimensional (3D) structures with resolution comparable to experimental results. Comparative modeling, which predicts the 3D structure of a protein based on its sequence similarity to homologous structures, is the most accurate computational method for structure prediction. In the last two decades, significant progress has been made on comparative modeling methods. Using the large number of protein structures deposited in the Protein Data Bank (∼65,000), automatic prediction pipelines are generating a tremendous number of models (∼1.9 million) for sequences whose structures have not been experimentally determined. Accurate models are suitable for a wide range of applications, such as prediction of protein binding sites, prediction of the effect of protein mutations, and structure-guided virtual screening. In particular, comparative modeling has enabled structure-based drug design against protein targets with unknown structures. In this review, we describe the theoretical basis of comparative modeling, the available automatic methods and databases, and the algorithms to evaluate the accuracy of predicted structures. Finally, we discuss relevant applications in the prediction of important drug target proteins, focusing on the G protein-coupled receptor (GPCR) and protein kinase families.
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Cite this article as:
Liu Tianyun, W. Tang Grace and Capriotti Emidio, Comparative Modeling: The State of the Art and Protein Drug Target Structure Prediction, Combinatorial Chemistry & High Throughput Screening 2011; 14 (6) . https://dx.doi.org/10.2174/138620711795767811
DOI https://dx.doi.org/10.2174/138620711795767811 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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