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

被引:19
作者
Lee, H
Kandasamy, SK
Larson, RG [1 ]
机构
[1] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Mech Engn & Macromol Sci & Engn Program, Ann Arbor, MI 48109 USA
关键词
D O I
10.1529/biophysj.105.066241
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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 similar to 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.
引用
收藏
页码:3807 / 3821
页数:15
相关论文
共 49 条
[1]  
BALLARD PL, 1995, PEDIATRICS, V96, P1046
[2]   GROMACS - A MESSAGE-PASSING PARALLEL MOLECULAR-DYNAMICS IMPLEMENTATION [J].
BERENDSEN, HJC ;
VANDERSPOEL, D ;
VANDRUNEN, R .
COMPUTER PHYSICS COMMUNICATIONS, 1995, 91 (1-3) :43-56
[3]   MOLECULAR-DYNAMICS WITH COUPLING TO AN EXTERNAL BATH [J].
BERENDSEN, HJC ;
POSTMA, JPM ;
VANGUNSTEREN, WF ;
DINOLA, A ;
HAAK, JR .
JOURNAL OF CHEMICAL PHYSICS, 1984, 81 (08) :3684-3690
[4]   Synthetic mimics of surfactant proteins B and C: In vitro surface activity and effects on lung compliance in two animal models of surfactant deficiency [J].
Bruni, R ;
Hernandez-Juviel, JM ;
Tanoviceanu, R ;
Walther, FJ .
MOLECULAR GENETICS AND METABOLISM, 1998, 63 (02) :116-125
[5]   TARGETED DISRUPTION OF THE SURFACTANT PROTEIN-B GENE DISRUPTS SURFACTANT HOMEOSTASIS, CAUSING RESPIRATORY-FAILURE IN NEWBORN MICE [J].
CLARK, JC ;
WERT, SE ;
BACHURSKI, CJ ;
STAHLMAN, MT ;
STRIPP, BR ;
WEAVER, TE ;
WHITSETT, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :7794-7798
[6]   PULMONARY SURFACTANT PROTEIN-B (SP-B) - STRUCTURE-FUNCTION-RELATIONSHIPS [J].
COCHRANE, CG ;
REVAK, SD .
SCIENCE, 1991, 254 (5031) :566-568
[7]   THE ROLE OF PALMITIC ACID IN PULMONARY SURFACTANT - ENHANCEMENT OF SURFACE-ACTIVITY AND PREVENTION OF INHIBITION BY BLOOD PROTEINS [J].
COCKSHUTT, AM ;
ABSOLOM, DR ;
POSSMAYER, F .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1085 (02) :248-256
[8]   Surfactant protein B: Effects on lipid domain formation and intermembrane lipid flow [J].
Creuwels, LAJM ;
vanGolde, LMG ;
Haagsman, HP .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1996, 1285 (01) :1-8
[9]   MOLECULAR-DYNAMICS SIMULATION OF A SMECTIC LIQUID-CRYSTAL WITH ATOMIC DETAIL [J].
EGBERTS, E ;
BERENDSEN, HJC .
JOURNAL OF CHEMICAL PHYSICS, 1988, 89 (06) :3718-3732
[10]   A SMOOTH PARTICLE MESH EWALD METHOD [J].
ESSMANN, U ;
PERERA, L ;
BERKOWITZ, ML ;
DARDEN, T ;
LEE, H ;
PEDERSEN, LG .
JOURNAL OF CHEMICAL PHYSICS, 1995, 103 (19) :8577-8593