-sheet containment by flanking prolines: Molecular Dynamic Simulations of the inhibition of -sheet elongation by proline residues in human prion protein

¹ Universiti Teknologi Malaysia
² Oxford University

^* To whom correspondence should be addressed. E-mail: dalby{at}stats.ox.ac.uk.

Submitted on June 27, 2006
Revised on July 31, 2006
Accepted on 16 November 2006

	Abstract

Previous molecular dynamic simulations have reported elongation of the existing -sheet in prion proteins. Detailed examination has shown that these elongations do not extend beyond the proline residues flanking these -sheets. In addition, proline has also been suggested to possess a possible structural role in preserving protein interaction sites by preventing invasion of neighbouring secondary structures. In this paper we have studied the possible structural role of the flanking proline residues by simulating mutant structures with alternate substitution of the proline residues with valine. Simulations showed a directional inhibition of elongation with the elongation progressing in the direction of valine including evident inhibition of elongation by existing proline residues. This suggests that the flanking Proline residues in prion proteins may have a containment role and would confine the -sheet within a specific length.

Key Words: Molecular dynamics, Prion protein, Prolines