Title

The Knob-Socket Model: A Novel Method for Predicting Protein Tertiary Structure

Poster Number

11B

Lead Author Major

Biochemistry

Lead Author Status

Senior

Second Author Major

Biology

Second Author Status

Junior

Third Author Major

Biology

Third Author Status

Senior

Format

Poster Presentation

Faculty Mentor Name

Jerry Tsai

Faculty Mentor Email

Jtsai@pacific.edu

Faculty Mentor Department

Chemistry

Graduate Student Mentor Name

Taylor Crawford

Graduate Student Mentor Email

t_rabara@u.pacific.edu

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

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Apr 29th, 1:00 PM Apr 29th, 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.