Molecular dynamics simulations of the anchoring and tilting of the lung-surfactant peptide SP-B1-25 in palmitic acid monolayers.

Abstract:

:We have performed molecular dynamics simulations of multiple copies of the lung-surfactant peptide SP-B1-25 in a palmitic acid (PA) monolayer. SP-B1-25 is a shorter version of lung-surfactant protein B, an important component of lung surfactant. Up to 30 ns simulations of 20 wt % SP-B1-25 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 degrees approximately 62 degrees with respect to the monolayer normal, similar to those measured experimentally by Lee et al. (Biophysical Journal. 2001. Synchrotron x-ray study of lung surfactant-specific protein SP-B in lipid monolayers. 81:572-585). 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 Arg-12 and Arg-17 and the hydrogen bond acceptors of the ionized PA headgroup, and the tilt angle is affected by the interactions of Tyr-7 and Gln-19 with the PA headgroup. Our work indicates that the factors controlling orientation of small peptides in lipid layers can now be uncovered through molecular dynamics simulations.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Lee H,Kandasamy SK,Larson RG

doi

10.1529/biophysj.105.066241

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

3807-21

issue

6

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(05)73024-1

journal_volume

89

pub_type

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