Novel computational methods for modeling backbone flexibility and improving side-chain prediction for protein design applications
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Authors
Schenkelberg, Christian Dane
Issue Date
2016-05
Type
Electronic thesis
Thesis
Thesis
Language
ENG
Keywords
Biochemistry and biophysics
Alternative Title
Abstract
This manuscript presents several computational landmarks in the development of the Plastic protein design algorithm. First, the Plastic protein design methodology is discussed, implemented, and evaluated for so-called “global” and “local” scoring schemes. The limitations of these scoring approaches are discussed. Second, a study in the effectiveness of modeling proteins as structural ensembles is presented and discussed. Plasticity depends very heavily on the reliability of structural ensembles to sample backbone space that is compatible with real primary sequences, so this study has direct implications for Plastic protein design. Third, an application of multiple-template protein design involving redesigning green fluorescent protein (GFP) to function as a programmable biosensor against pathogens is discussed. One significant aim of computational research involves testing its applicability to real experimental problems. The biosensor project is an ideal candidate for this aim because preliminary data suggests that one source of error in the GFP biosensor design process concerns failure to model multiple states of the GFP chromophore maturation pathway. Lastly, a project involving the creation of a sophisticated graphical user interface (GUI) for the Rosetta modeling suite, named “InteractiveROSETTA”, is presented. The final chapter discusses some future direction for both the Plastic protein design project and the InteractiveROSETTA project.
Description
May 2016
School of Science
School of Science
Full Citation
Publisher
Rensselaer Polytechnic Institute, Troy, NY