The Knob-Socket Model: A Novel Method for Predicting Protein Tertiary Structure
Poster Number
11B
Format
Poster Presentation
Faculty Mentor Name
Jerry Tsai
Faculty Mentor Department
Chemistry
Graduate Student Mentor Name
Taylor Crawford
Graduate Student Mentor Department
Chemistry
Abstract/Artist Statement
The novel knob-socket model provides a basis for defining how sequence determines protein structure. This model describes a four-residue tetrahedral motif: a single amino acid residue “knob” from one secondary structure element that packs into a three amino acid residue “socket” from another piece of secondary structure. Specifically, we analyzed the capabilities of the knob-socket construct in ⍺-helical protein packing. The knob-socket model provides a method of predicting intra- and inter-helical interactions based on amino acid side chains. Sockets can be categorized into three different groups: (1) free, unpacked and favoring intra-helical interactions, (2) filled, packed with a knob, and favoring inter-helical interactions, and (3) non, disfavoring alpha-helical packing. Using the PDB database, free and filled propensity libraries were developed to assign numerical probabilities to each combination of 3 amino acids in a socket. The propensities of the three residue sockets then served as an amino acid sequence code for alpha-helical packing interactions. This amino acid code allowed for the de novo design of an ⍺-helical antiparallel homodimer called KS⍺1.1. The structure of KS⍺1.1 and its dimerization was investigated using point mutations via site-directed mutagenesis. Based on propensities from the knob-socket model, we were able to predict how the point mutations will affect helix stability. These predictions were then confirmed via analysis with circular dichroism spectroscopy.
Location
DeRosa University Center, Ballroom
Start Date
29-4-2017 1:00 PM
End Date
29-4-2017 3:00 PM
The Knob-Socket Model: A Novel Method for Predicting Protein Tertiary Structure
DeRosa University Center, Ballroom
The novel knob-socket model provides a basis for defining how sequence determines protein structure. This model describes a four-residue tetrahedral motif: a single amino acid residue “knob” from one secondary structure element that packs into a three amino acid residue “socket” from another piece of secondary structure. Specifically, we analyzed the capabilities of the knob-socket construct in ⍺-helical protein packing. The knob-socket model provides a method of predicting intra- and inter-helical interactions based on amino acid side chains. Sockets can be categorized into three different groups: (1) free, unpacked and favoring intra-helical interactions, (2) filled, packed with a knob, and favoring inter-helical interactions, and (3) non, disfavoring alpha-helical packing. Using the PDB database, free and filled propensity libraries were developed to assign numerical probabilities to each combination of 3 amino acids in a socket. The propensities of the three residue sockets then served as an amino acid sequence code for alpha-helical packing interactions. This amino acid code allowed for the de novo design of an ⍺-helical antiparallel homodimer called KS⍺1.1. The structure of KS⍺1.1 and its dimerization was investigated using point mutations via site-directed mutagenesis. Based on propensities from the knob-socket model, we were able to predict how the point mutations will affect helix stability. These predictions were then confirmed via analysis with circular dichroism spectroscopy.