Bilayer-Peptide Interactions

Damodaran, Krishnan; MerzJr., Kenneth M.

doi:10.1007/978-1-4684-8580-6_11

Cited by 2 publications

(6 citation statements)

References 69 publications

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“…The model has several additional shortcomings. For example, our assumption that the bilayer surface is rigid and does not change its structure when the toxins bind is probably incorrect: molecular dynamics and Monte Carlo simulations indicate that the polar head groups are flexible (e.g., Pastor, 1994) and that interactions with proteins may perturb the structure (e.g., Zhou and Schulten, 1995;Woolf and Roux, 1996;Damodaran and Merz, 1996). The "soft" or nonrigid nature of the bilayer surface may strongly affect the calculations of the short-range Born and nonpolar interactions, but should have a much smaller effect on the calculation of the long-range Coulomb attraction.…”

Section: Discussionmentioning

confidence: 99%

Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles

Ben‐Tal

Miller

McLaughlin

1997

Biophysical Journal

144

145

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We previously applied the Poisson-Boltzmann equation to atomic models of phospholipid bilayers and basic peptides to calculate their electrostatic interactions from first principles (Ben-Tal, N., B. Honig, R. M. Peitzsch, G. Denisov, and S. McLaughlan. 1996. Binding of small basic peptides to membranes containing acidic lipids. Theoretical models and experimental results. Biophys. J. 71:561-575). Specifically, we calculated the molar partition coefficient, K (the reciprocal of the lipid concentration at which 1/2 the peptide is bound), of simple basic peptides (e.g., pentalysine) with phospholipid vesicles. The theoretical predictions agreed well with experimental measurements of the binding, but the agreement could have been fortuitous because the structure(s) of these flexible peptides is not known. Here we use the same theoretical approach to calculate the membrane binding of two small proteins of known structure: charybdotoxin (CTx) and iberiotoxin (IbTx); we also measure the binding of these proteins to phospholipid vesicles. The theoretical model describes accurately the dependence of K on the ionic strength and mol % acidic lipid in the membrane for both CTx (net charge +4) and IbTx (net charge +2). For example, the theory correctly predicts that the value of K for the binding of CTx to a membrane containing 33% acidic lipid should decrease by a factor of 10(5) when the salt concentration increases from 10 to 200 mM. We discuss the limitations of the theoretical approach and also consider a simple extension of the theory that incorporates nonpolar interactions.

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Section: Discussionmentioning

confidence: 99%

Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles

Ben‐Tal

Miller

McLaughlin

1997

Biophysical Journal

144

145

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“…Although constant pressure simulations are desirable in bilayer simulations, a recent 10-ns constant volume simulation on DPPC bilayers has shown that the system remained stable throughout the simulation (Essmann and Berkowitz, 1999). Many of the peptide bilayer simulations have been carried out successfully in the NVE ensemble (Berneche et al, 1998;Woolf, 1997;Damodaran and Merz, 1996;Ha Duong et al, 1999;Huang and Loew, 1995).…”

Section: Methodsmentioning

confidence: 99%

“…Construction of the NVE ensemble requires a reasonable estimate of the cross-sectional area of the system. The value considered for the DMPC cross-sectional area ranged from 61 to 66 Å 2 in previous simulation studies (Chiu et al, 1999b;Woolf, 1997;Shen et al, 1997;Damodaran and Merz, 1996;Essmann and Berkowitz, 1999). In the present simulations, we have taken the crosssectional area of DMPC to be 63.1 Å 2 .…”

Section: Initial Structuresmentioning

confidence: 99%

“…1996; Damodaran and Merz, 1996;Shen et al, 1997;Chiu et al, 1999a;Ha Duong et al, 1999). The distribution of peptide extends from the bulk water to the center of the bilayer in the positive z axis (top layer).…”

Section: Density Profilesmentioning

confidence: 99%

“…Studies of peptides in explicit bilayers with molecular dynamics (MD) simulations have produced details related to various biological mechanisms. Examples include the characterization of gramicidin channels (Woolf and Roux, 1996;Chiu et al, 1999b,c), the two-stage model of membrane protein folding in bacteriorhodopsin helices (Woolf, 1997(Woolf, , 1998a, the mechanism of membrane lysis caused by melittin (Berneche et al, 1998;Bachar and Becker, 1999), the action of small fusion-inhibiting peptides (Damodaran and Merz, 1996), and the stability of the channel formed by alamethicin helix bundles (Tieleman et al, 1999). The importance of residues bridging the transmembrane and surface-bound helical segments in bacteriophage Pf1 coat protein (Roux and Woolf, 1996) and the role of the Asn-Pro motif in the seventh transmembrane segment of 5HT 2A receptor (Ha Duong et al, 1999) have also been described from such detailed MD simulations.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Dynamics Simulations Predict a Tilted Orientation for the Helical Region of Dynorphin A(1–17) in Dimyristoylphosphatidylcholine Bilayers

Sankararamakrishnan

Weinstein

2000

Biophysical Journal

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The structural properties of the endogenous opioid peptide dynorphin A(1-17) (DynA), a potential analgesic, were studied with molecular dynamics simulations in dimyristoylphosphatidylcholine bilayers. Starting with the known NMR structure of the peptide in dodecylphosphocholine micelles, the N-terminal helical segment of DynA (encompassing residues 1-10) was initially inserted in the bilayer in a perpendicular orientation with respect to the membrane plane. Parallel simulations were carried out from two starting structures, systems A and B, that differ by 4 A in the vertical positioning of the peptide helix. The complex consisted of approximately 26,400 atoms (dynorphin + 86 lipids + approximately 5300 waters). After >2 ns of simulation, which included >1 ns of equilibration, the orientation of the helical segment of DynA had undergone a transition from parallel to tilted with respect to the bilayer normal in both the A and B systems. When the helix axis achieved a approximately 50 degrees angle with the bilayer normal, it remained stable for the next 1 ns of simulation. The two simulations with different starting points converged to the same final structure, with the helix inserted in the bilayer throughout the simulations. Analysis shows that the tilted orientation adopted by the N-terminal helix is due to specific interactions of residues in the DynA sequence with phospholipid headgroups, water, and the hydrocarbon chains. Key elements are the "snorkel model"-type interactions of arginine side chains, the stabilization of the N-terminal hydrophobic sequence in the lipid environment, and the specific interactions of the first residue, Tyr. Water penetration within the bilayer is facilitated by the immersed DynA, but it is not uniform around the surface of the helix. Many water molecules surround the arginine side chains, while water penetration near the helical surface formed by hydrophobic residues is negligible. A mechanism of receptor interaction is proposed for DynA, involving the tilted orientation observed from these simulations of the peptide in the lipid bilayer.

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Bilayer-Peptide Interactions

Cited by 2 publications

References 69 publications

Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles

Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles

Molecular Dynamics Simulations Predict a Tilted Orientation for the Helical Region of Dynorphin A(1–17) in Dimyristoylphosphatidylcholine Bilayers

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