Theoretically determined three-dimensional structure for the repeating tetrapeptide unit of the circumsporozoite coat protein of the malaria parasite Plasmodium falciparum.

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Abstract
A model for the three-dimensional structure of the repeating Asn-Pro-Asn-Ala tetrapeptide of the immunodominant circumsporozoite protein of Plasmodium falciparum has been developed. A trial structure in the form of a type I .beta. turn with asparagine side chains hydrogen-bounded to the backbone peptide linkages was used as a starting point. A repeating oligomer of this trial structure was modeled using energy minimization and molecular dynamics computer simulations in conjuction with image boundary conditions. The most stable structure generated is a right-handed 1238 helix, which is unlike any previously identified protein secondary structure. The helix has 12 residues per turn, corresponding to an angle of twist of 120.degree. per tetrapeptide unit, and a pitch of 4.95 .ANG., corresponding to a rise of 1.65 .ANG. per tetrapeptide unit. It is highly stabilized by extensive hydrogen bonding, with each tetrapeptide unit acting as an acceptor for five hydrogen bonds and as a donor for five hydrogen bonds to residues in adjacent turns as well as having four weak internal hydrogen bonds. A number of nearly isoenergetic variations on the most stable structure that still retained the basic 1238 helical motif were also discovered. The implications of these structure for vaccine development are discussed.