Characterizing Tertiary Packing Surfaces with the Knob-Socket Model
Poster Number
27
Introduction/Abstract
Understanding how the sequence of amino acids folds into a three-dimensional protein structure is termed is the protein folding problem. One difficult aspect of the protein-folding problem is the characterization of the non-specific interactions that define packing in protein tertiary structure. It has been previously shown that a tetrahedral packing motif, the knob-socket, is robust enough to capture the essential features of packing in protein structure. The knob-socket is comprised of three residues, local in sequence to each other, forming a socket that packs with an amino acid (the knob) far away in sequence, yet close in space to the socket residues.
Purpose
To better understand protein structure, this work extends the knob-socket model by classifying the interactions of a single knob packed into a set of contiguous sockets, or a pocket.
Method
In an analysis of α-helices and β- sheets, the positions of the amino acids comprising pockets are projected onto two-dimensional, repetitive lattices defined by the knob-socket model. Using this approach, the variety of pocket shapes is investigated in order to better understand the tertiary packing surfaces in proteins.
Results
The diversity of pocket geometries can be organized into groups of pockets that share a common core, which suggests that some interactions in pockets are ancillary to packing. Further analysis of pocket geometries displays a preferred configuration that is right-handed in α-helices and lefthanded in β-sheets. The amino acid composition of pockets illustrates the importance of nonpolar amino acids in packing as well as position specificity. As expected, all pocket shapes prefer to pack with hydrophobic knobs; however, knobs are not selective for a certain type of pocket. Investigating side-chain rotamer preferences for certain pocket shapes uncovers no strong correlations.
Significance
These findings allow a simple vocabulary based on knobs and sockets to describe protein tertiary packing that supports improved analysis, design and prediction of protein structure.
Location
DeRosa University Center, Stockton campus, University of the Pacific
Format
Poster Presentation
Characterizing Tertiary Packing Surfaces with the Knob-Socket Model
DeRosa University Center, Stockton campus, University of the Pacific
Understanding how the sequence of amino acids folds into a three-dimensional protein structure is termed is the protein folding problem. One difficult aspect of the protein-folding problem is the characterization of the non-specific interactions that define packing in protein tertiary structure. It has been previously shown that a tetrahedral packing motif, the knob-socket, is robust enough to capture the essential features of packing in protein structure. The knob-socket is comprised of three residues, local in sequence to each other, forming a socket that packs with an amino acid (the knob) far away in sequence, yet close in space to the socket residues.
