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Comparative Modeling of Proteins

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Molecular Modeling of Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1215))

Abstract

Much of the biochemistry that underlies health, medicine, and numerous biotechnology applications is regulated by proteins, whereby the ability of proteins to effect such processes is dictated by the three-dimensional structural assembly of the proteins. Thus, a detailed understanding of biochemistry requires not only knowledge of the constituent sequence of proteins, but also a detailed understanding of how that sequence folds spatially. Three-dimensional analysis of protein structures is thus proving to be a critical mode of biological and medical discovery in the early twenty-first century, providing fundamental insight into function that produces useful biochemistry and dysfunction that leads to disease. The large number of distinct proteins precludes rigorous laboratory characterization of the complete structural proteome, but fortunately efficient in silico structure prediction is possible for many proteins that have not been experimentally characterized. One technique that continues to provide accurate and efficient protein structure predictions, called comparative modeling, has become a critical tool in many biological disciplines. The discussion herein is an updated version of a previous 2008 treatise focusing on the general philosophy of comparative modeling methods and on specific strategies for successfully achieving reliable and accurate models. The chapter discusses basic aspects of template selection, sequence alignment, spatial alignment, loop and gap modeling, side chain modeling, structural refinement and validation, and provides an important new discussion on automated computational tools for protein structure prediction.

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Abbreviations

AA:

Amino acid (plural: AAs)

BSE:

Bovine spongiform encephalopathy

CASP:

Critical assessment of techniques for protein structure prediction

CATH:

Class architecture, topology, and homologous superfamily

Cα :

Alpha carbon on the amino acid backbone

DNA:

Deoxyribonucleic acid

H-bond:

Hydrogen-bond

MD:

Molecular dynamics

NMR:

Nuclear magnetic resonance

NR :

Number of residues

PDB:

Protein data bank

PrPC:

Prion protein cellular

PrPSc:

Prion protein scrapie

ps:

Picosecond(s)

PSI:

Protein structure initiative

RMSD:

Root-mean-squared deviation

3D:

Three-dimensional

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Author information

Authors and Affiliations

  1. LiS Consulting, 2933 Lankford Drive, Lawrence, KS, 66046, USA

    Gerald H. Lushington

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  1. Gerald H. Lushington
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Correspondence to Gerald H. Lushington .

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Editors and Affiliations

  1. University of Hertfordshire, Hatfield, Hertfordshire, United Kingdom

    Andreas Kukol

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Lushington, G.H. (2015). Comparative Modeling of Proteins. In: Kukol, A. (eds) Molecular Modeling of Proteins. Methods in Molecular Biology, vol 1215. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1465-4_14

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  • DOI: https://doi.org/10.1007/978-1-4939-1465-4_14

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1464-7

  • Online ISBN: 978-1-4939-1465-4

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