Stabilising Non-Polar/Polar Side Chain Interactions in the α-Helix

2000 ◽  
Vol 28 (3) ◽  
pp. A72-A72
Author(s):  
Charles D. Andrew ◽  
Simon Penel ◽  
Gareth R. Jones ◽  
Andrew J. Doig
Keyword(s):  
Side Chain ◽  
Α Helix

Structure, stability and folding of the α-helix

2001 ◽  
Vol 68 ◽  
pp. 95-110 ◽  
Author(s):  
Andrew J. Doig ◽  
Charles D. Andrew ◽  
Duncan A. E. Cochran ◽  
Eleri Hughes ◽  
Simon Penel ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Hydrophobic Interactions ◽  
Data Bank ◽  
Site Directed Mutagenesis ◽  
Model Systems ◽  
Side Chain ◽  
Structure Stability ◽  
Helical Peptides ◽  
Vast Number ◽  
Α Helix

Pauling first described the α-helix nearly 50 years ago, yet new features of its structure continue to be discovered, using peptide model systems, site-directed mutagenesis, advances in theory, the expansion of the Protein Data Bank and new experimental techniques. Helical peptides in solution form a vast number of structures, including fully helical, fully coiled and partly helical. To interpret peptide results quantitatively it is essential to use a helix/coil model that includes the stabilities of all these conformations. Our models now include terms for helix interiors, capping, side-chain interactions, N-termini and 310-helices. The first three amino acids in a helix (N1, N2 and N3) and the preceding N-cap are unique, as their amide NH groups do not participate in backbone hydrogen bonding. We surveyed their structures in proteins and measured their amino acid preferences. The results are predominantly rationalized by hydrogen bonding to the free NH groups. Stabilizing side-chain-side-chain energies, including hydrophobic interactions, hydrogen bonding and polar/non-polar interactions, were measured accurately in helical peptides. Helices in proteins show a preference for having approximately an integral number of turns so that their N- and C-caps lie on the same side. There are also strong periodic trends in the likelihood of terminating a helix with a Schellman or αL C-cap motif. The kinetics of α-helix folding have been studied with stopped-flow deep ultraviolet circular dichroism using synchrotron radiation as the light source; this gives a far superior signal-to-noise ratio than a conventional instrument. We find that poly(Glu), poly(Lys) and alanine-based peptides fold in milliseconds, with longer peptides showing a transient overshoot in helix content.

scholarly journals LK peptide side chain dynamics at interfaces are independent of secondary structure

2017 ◽  
Vol 19 (42) ◽  
pp. 28507-28511 ◽  
Author(s):  
Michael A. Donovan ◽  
Helmut Lutz ◽  
Yeneneh Y. Yimer ◽  
Jim Pfaendtner ◽  
Mischa Bonn ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Real Time ◽  
Surface Interactions ◽  
Side Chain ◽  
Chain Dynamics ◽  
Air Interface ◽  
Time Observation ◽  
Α Helix ◽  
Side Chain Dynamics ◽  
Real Time Observation

Real-time observation of the ultrafast motions of leucine side chains within model peptides at the water–air interface with representative folds – α-helix, 310-helix, β-strand – show that interfacial dynamics are mostly determined by surface interactions.

scholarly journals Enhancement of α-Helix Mimicry by an α/β-Peptide Foldamer via Incorporation of a Dense Ionic Side-Chain Array

2012 ◽  
Vol 134 (17) ◽  
pp. 7317-7320 ◽  
Author(s):  
Lisa M. Johnson ◽  
David E. Mortenson ◽  
Hyun Gi Yun ◽  
W. Seth Horne ◽  
Thomas J. Ketas ◽  
...  
Keyword(s):  
Side Chain ◽  
Α Helix

scholarly journals Addition of side-chain interactions to 310-helix/coil and α-helix/310-helix/coil theory

1998 ◽  
Vol 7 (11) ◽  
pp. 2374-2383 ◽  
Author(s):  
Jia Ke Sun ◽  
Andrew J. Doig
Keyword(s):  
Side Chain ◽  
Α Helix ◽  
310 Helix

Simulation of Monomers Selection on Single-Molecular Copolymer Nano-Particles that Mimic Protein Folding

2012 ◽  
Vol 496 ◽  
pp. 58-61
Author(s):  
Wei Zhang
Keyword(s):  
Protein Folding ◽  
Stable Structure ◽  
Nano Particles ◽  
Side Chain ◽  
Nano Particle ◽  
Hp Model ◽  
Α Helix ◽  
Selection Of

The synthesis of protein-like single molecular nano-particle can be simplified by use fewer but longer monomers, which correspond to several old short monomers. The selection of new long monomer subset is optimized and tested in HP model and other models. Results show 2-3 types new monomer are enough to build stable structure, and long monomers should include integer length of one helix, and with interlaced hydrophobic and polar side-chain, thus can form α-helix like structure.

α-Helix mimetics as inhibitors of protein–protein interactions

2008 ◽  
Vol 36 (6) ◽  
pp. 1414-1417 ◽  
Author(s):  
Ishu Saraogi ◽  
Andrew D. Hamilton
Keyword(s):  
Protein Interactions ◽  
First Generation ◽  
Side Chain ◽  
Protein Protein Interactions ◽  
Substitution Pattern ◽  
Pathological Conditions ◽  
Synthetic Accessibility ◽  
Helix Mimetics ◽  
Viable Approach ◽  
Α Helix

The inhibition of protein–protein interactions using small molecules is a viable approach for the treatment of a range of pathological conditions that result from a malfunctioning of these interactions. Our strategy for the design of such agents involves the mimicry of side-chain residues on one face of the α-helix; these residues frequently play a key role in mediating protein–protein interactions. The first-generation terphenyl scaffold, with a 3,2′,2″-substitution pattern, is able to successfully mimic key helix residues and disrupt therapeutically relevant interactions, including the Bcl-XL–Bak and the p53–hDM2 (human double minute 2) interactions that are implicated in cancer. The second- and third-generation scaffolds have resulted in greater synthetic accessibility and more drug-like character in these molecules.

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