The design of linear peptides that fold as monomeric beta-sheet structures.

Abstract:

:Current knowledge about the determinants of beta-sheet formation has been notably improved by the structural and kinetic analysis of model peptides, by mutagenesis experiments in proteins and by the statistical analysis of the protein structure database (Protein Data Bank; PDB). In the past year, several peptides comprising natural and non-natural amino acids have been designed to fold as monomeric three-stranded beta-sheets. In all these cases, the design strategy has involved both the statistical analysis of the protein structure database and empirical information obtained in model beta-hairpin systems and in proteins. Only in one case was rotamer analysis performed to check for the compatibility of the sidechain packing. It is foreseeable that, in future designs, algorithms exploring the sequence and conformational space will be employed. For the design of small proteins (less than 30 amino acids), questions remain about the demonstration of two-state behavior, the formation of a well-defined network of mainchain hydrogen bonds and the quantification of the structured populations.

journal_name

Curr Opin Struct Biol

authors

Lacroix E,Kortemme T,Lopez de la Paz M,Serrano L

doi

10.1016/s0959-440x(99)80069-4

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

487-93

issue

4

eissn

0959-440X

issn

1879-033X

pii

sb9408

journal_volume

9

pub_type

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