Gerald Lushington | Kansas State University (original) (raw)

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Papers by Gerald Lushington

Methods in molecular biology, 2008

Three-dimensional analysis of protein structures is proving to be one of the most fruitful modes ... more Three-dimensional analysis of protein structures is proving to be one of the most fruitful modes of biological and medical discovery in the early 21st century, providing fundamental insight into many (perhaps most) biochemical functions of relevance to the cause and treatment of diseases. Fully realizing such insight, however, would require analysis of too many distinct proteins for thorough laboratory analysis of all proteins to be feasible, thus, any method capable of accurate, efficient in silico structure prediction should prove highly expeditious. The technique generally acknowledged to provide the most accurate protein structure predictions, called comparative modeling, has, thus, attracted substantial attention and is the focus of this chapter. Although other reviews have reported on the method development and research history of comparative modeling, our discussion herein focuses on the general philosophy of the method and specific strategies for successfully achieving reliable and accurate models. The chapter, thus, relates aspects of template selection, sequence alignment, spatial alignment, loop and gap modeling, side chain modeling, structural refinement, and validation.

Journal of combinatorial chemistry, Sep 29, 2010

Bioorganic & Medicinal Chemistry Letters, Sep 1, 2011

Bioorganic & Medicinal Chemistry, 2013

European journal of medicinal chemistry, 2018

Springer eBooks, Sep 3, 2014

Much of the biochemistry that underlies health, medicine, and numerous biotechnology applications... more 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.