Molecular dynamics simulations of the anchoring and tilting of the lung-surfactant peptide SP-B_{1- 25} in palmitic acid monolayers

¹ University of Michigan

^* To whom correspondence should be addressed. E-mail: rlarson{at}umich.edu.

Submitted on May 11, 2005
Revised on August 16, 2005
Accepted on 31 August 2005

	Abstract

We have performed molecular dynamics simulations of multiple copies of the lung-surfactant peptide SP-B_1-25 in a palmitic acid (PA) monolayer. SP-B_1-25 is a shorter version of lung surfactant protein B, an important component of lung surfactant. Up to 30ns simulations of 20 wt% SP-B_1-25 in the PA monolayers were performed with different surface areas of PA, extents of PA ionization, and various initial configurations of the peptides. Starting with initial peptide orientation perpendicular to the monolayer, the predicted final tilt angles average 54°~62° with respect to the monolayer normal, similar to those measured experimentally by Lee et al. (Biophys. J. 81:572-585, 2001). In their final conformations, hydrogen-bond analysis and amino acid mutation studies show that the peptides are anchored by hydrogen bond interactions between the cationic residues Arg12 and Arg17 and the hydrogen bond acceptors of the ionized PA head group, and the tilt angle is affected by the interactions of Tyr7 and Gln19 with the PA head group. Our work indicates that the factors controlling orientation of small peptides in lipid layers can now be uncovered through molecular dynamics simulations.

Key Words: Lung surfactant peptide SP-B, Molecular dynamics simulation, Palmitic acid monolayers, protein-lipid interaction

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