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Explorations into protein structure with the knob-socket model

Author

Keith Jeffrey Fraga, University of the Pacific

Date of Award

2016

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Jerry Tsai

First Committee Member

Xiaoling Li

Second Committee Member

Michael McCallum

Abstract

Protein sequences contain the information in order for a protein to fold to a unique compact, three-dimensional native structure. The forces that drive protein structures to form compact folds are largely dominated by burial of hydrophobic amino acids, which results in non-specific packing of amino acid side-chains. The knob-socket model attempts to organize side-chain packing into tetrahedral packing motifs. This tetrahedral motif is characterized with a three residues on the same secondary structure forming the base of the tetrahedron packing with a side-chain from a separate secondary structure. The base of the motif is termed the socket, and the other side-chain is called the knob. Here, we focus on extending the knob-socket model to understand tertiary and quaternary structure. First, single knobs sometimes pack into more than one socket in real structures. We focus on understanding the topology and amino acid preferences of these tertiary packing surfaces. The main results from the study of tertiary packing surfaces is that they have a preferred handedness, some interactions are ancillary to the packing interaction, there are specific amino preferences for specific positions in packing surfaces, and there is no relationship between side-chain rotamer of the knob packing into the tertiary packing surface. Next, we examine the application of the knob-socket to irregular and mixed packing in protein structure. The main conclusions from these efforts show canonical packing modes between secondary structures and highlight the important of coil secondary structure in providing many of the knobs for packing. Third, we investigate protein quaternary structure with a clique analysis of side-chain interactions. We identify a possible pseudo knob-socket interaction, and compare knob-socket interactions between tertiary and quaternary structure. Lastly, we discuss the workflow used in CASP12 to predict side-chain contacts and atomic coordinates of proteins.

Pages

151

ISBN

9781369117325

Recommended Citation

Fraga, Keith Jeffrey. (2016). Explorations into protein structure with the knob-socket model. University of the Pacific, Thesis - Pacific Access Restricted. https://scholarlycommons.pacific.edu/uop_etds/264

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.