Title

Minimal amino acid sequence supporting a gross fold within a protein.

Presentation Type

Poster

Abstract

Proteins are the powerhouse of cellular activity. These dynamic tools manipulate biological molecules, initiate communication between cells, transport molecules, and much more. These macromolecules are encoded by strings of amino acids that dictate the three-dimensional structure of a folded protein. Specifically, our research focuses on the minimal amino acid sequence necessary to establish a gross fold. Modeling with the Monte Carlo (MC) sampling software CAMPARI, we are able to simulate a simple peptide structure: a 42-residue polyalanine with dispersed lysines (polyAK or (A5K)7). Polyalanine is known to form long alpha helices with no tertiary interactions. Insertion of a proline segment within the middle of this structure creates the bridge between the linear polyAK and a two-helix bundle, 3D arrangement (polyAKPSDP or (A5K)3(PSDPAK)(A5K)3). The PSDP sequence creates a turn within the two-helix bundle needle proteins found in type 3 secretion systems, such as that seen within the pathogenic bacteria, Shigella flexneri. As expected, MC simulations show that polyAK prefers an alpha helical conformation. PolyAKPSDP, as hoped, favors a two-helix bundle. Leucines in the two-helix bundle needle proteins in nature stabilize the bundle through both short and long-range interactions. MC simulations show that short-range interactions between hydrophobic leucine residues added to polyAKPSDP reinforce its 3D structure. Each peptide was simulated over a range of temperatures, and the structure was evaluated through the radius of gyration, secondary structure content, contact maps, helicity, and other structural measures. Once those tests were complete, we compared polyAKPSDP and polyAK using a clustering algorithm embedded in the CAMPARI software. Future investigations will involve investigating the effect of long-range contacts on the turn.

Category

Physical Sciences

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Apr 11th, 11:00 AM Apr 11th, 12:00 PM

Minimal amino acid sequence supporting a gross fold within a protein.

Proteins are the powerhouse of cellular activity. These dynamic tools manipulate biological molecules, initiate communication between cells, transport molecules, and much more. These macromolecules are encoded by strings of amino acids that dictate the three-dimensional structure of a folded protein. Specifically, our research focuses on the minimal amino acid sequence necessary to establish a gross fold. Modeling with the Monte Carlo (MC) sampling software CAMPARI, we are able to simulate a simple peptide structure: a 42-residue polyalanine with dispersed lysines (polyAK or (A5K)7). Polyalanine is known to form long alpha helices with no tertiary interactions. Insertion of a proline segment within the middle of this structure creates the bridge between the linear polyAK and a two-helix bundle, 3D arrangement (polyAKPSDP or (A5K)3(PSDPAK)(A5K)3). The PSDP sequence creates a turn within the two-helix bundle needle proteins found in type 3 secretion systems, such as that seen within the pathogenic bacteria, Shigella flexneri. As expected, MC simulations show that polyAK prefers an alpha helical conformation. PolyAKPSDP, as hoped, favors a two-helix bundle. Leucines in the two-helix bundle needle proteins in nature stabilize the bundle through both short and long-range interactions. MC simulations show that short-range interactions between hydrophobic leucine residues added to polyAKPSDP reinforce its 3D structure. Each peptide was simulated over a range of temperatures, and the structure was evaluated through the radius of gyration, secondary structure content, contact maps, helicity, and other structural measures. Once those tests were complete, we compared polyAKPSDP and polyAK using a clustering algorithm embedded in the CAMPARI software. Future investigations will involve investigating the effect of long-range contacts on the turn.