lec24 - Molecular Simulations of Proteins and Peptides...

Info iconThis preview shows pages 1–11. Sign up to view the full content.

View Full Document Right Arrow Icon
Molecular Simulations of Proteins and Peptides Types of simulations Protein Folding Aggregation
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Protein Folding History Diseases Energetics Models Prediction NC State University
Background image of page 2
Overview of Folding Inside a Cell 1. Protein synthesis occurs in the ribosome. 2. Folding can be aided by chaperones or can be spontaneous. 3-6. Dissociation and transport of folded proteins. 7-11. Degradation of misfolded proteins in the proteosome.
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Early work Basic structures (Pauling) α -helix and the β -sheet Proteins fold spontaneously (Anfinsen) This is a remarkable fact given that the number of possible protein conformational states is quite large. Early theory of folding (Levinthal) For a typical protein with 100 residues and 6 conformations per residue the total number of conformations possible is 6 100 . At a folding rate of one conformation per picosecond folding the time is longer than the age of the universe. These studies suggested that proteins have a trajectory or pathway.
Background image of page 4
The amino acids in an α helix are arranged in a helical structure, 0.54 nm wide. Each amino acid results in a 100° turn in the helix, and corresponds to a translation of 0.15 nanometres along the helical axis. The helix is tightly packed; there is almost no free space within the helix. All amino acid side-chains are arranged at the outside of the helix. The N-H group of amino acid (n+4) can establish a hydrogen bond with the C=O group of amino acid (n).
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
A β sheet consists of two or more amino acid sequences within the same protein that are arranged adjacently. They can be and in parallel or anti-parallel. The strands have an alternating orientation such that hydrogen bonds can form between the two strands. The N-H groups in the backbone of one strand bond with the C=O groups in the backbone of the adjacent strand(s). The strands stand 0.35 nm apart.
Background image of page 6
Both anti-parallel and parallel pleated β sheets are shown in the figure below. The turn region is also known as a β turn.
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
The Anfinsen experiment: spontaneous folding The seminal experiment reported by Anfinsen demonstrated that RNase A could be fully denatured by: 1. reducing the disulfide bonds (using β -mercaptoethanol) 2. dissolving in 8 M urea and then fully renatured on diluting out the urea and allowing the disulfides to reoxidize. Essentially full return of catalytic activity was obtained. This experiment demonstrated that all the information necessary to determine the three-dimensional fold was incorporated in the amino acid sequence. Anfinsen (1973) Science, 181 223
Background image of page 8
Background image of page 9

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
There are many diseases known to result from misfolding - Alzheimer's disease. - Cystic fibrosis. - Mad Cow disease. - Many cancers. Folding of peptide drugs is an important issue for biotechnology. The prediction of secondary and tertiary structure from the
Background image of page 10
Image of page 11
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 08/01/2008 for the course CHEM 596M taught by Professor Franzen during the Spring '08 term at N.C. State.

Page1 / 75

lec24 - Molecular Simulations of Proteins and Peptides...

This preview shows document pages 1 - 11. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online