On the formation of protein tertiary structure on a computer.
In this paper we carry out computer simulation studies of some of the factors responsible for protein tertiary structure. We show that it is possible to obtain (fold) a compact globular conformation from a sequence of amino acids consisting of only glycines and alanines. Our results indicate that glycines play a central role in stabilizing globular structures by facilitating the formation of turns and by destabilizing helical structures. Using this simple two-amino-acid representation, which serves as a control experiment, we are able to obtain a conformation that resembles the native structure of pancreatic trypsin inhibitor, as closely as any obtained previously in folding studies. However, careful examination reveals that the true chain topology has not been reproduced here or in previous studies. We suggest that the discrepancies between calculated and observed structures are more significant than the similarities. The implications of these results for the validity of models for protein folding, the use of pancreatic trypsin inhibitor in folding studies, and the possible role of glycine in the evolution of protein structure are discussed.
D000409:Alanine; D003201:Computers; D005998:Glycine; D011487:Protein Conformation
D000409:Alanine; D005998:Glycine
Angew Chem Int Ed Engl. 1977;16(1):23-32
402092
J Mol Biol. 1977 Jan 5;109(1):99-129
839535
J Mol Biol. 1976 Oct 5;106(4):983-94
978745
Nature. 1975 Feb 27;253(5494):694-8
1167625
Adv Protein Chem. 1975;29:205-300
237413
Cold Spring Harb Symp Quant Biol. 1972;36:141-8
4508131
J Am Chem Soc. 1974 Aug 21;96(17):5327-35
4851861
J Am Chem Soc. 1974 Aug 21;96(17):5319-27
4851860
Proc Natl Acad Sci U S A. 1976 Jun;73(6):1974-8
1064867
J Mol Biol. 1976 Jun 14;104(1):59-107
957439
Proc Natl Acad Sci U S A. 1975 Apr;72(4):1221-5
1055397
Proc Natl Acad Sci U S A. 1975 Oct;72(10):3802-6
1060065
J Mol Biol. 1975 Jun 25;95(2):167-99
1185779
Arch Biochem Biophys. 1971 Jun;144(2):453-61
5569892