prosECCo75 is an optimized force field effectively incorporating electronic polarization via charge scaling. It aims to enhance the accuracy of nominally nonpolarizable molecular dynamics simulations for interactions in biologically relevant systems involving water, ions, proteins, lipids, and saccharides. Recognizing the inherent limitations of nonpolarizable force fields in precisely modeling electrostatic interactions essential for various biological processes, we mitigate these shortcomings by accounting for electronic polarizability in a physically rigorous mean-field way that does not add to computational costs. With this scaling of (both integer and partial) charges within the CHARMM36 framework, prosECCo75 addresses overbinding artifacts. This improves agreement with experimental ion binding data across a broad spectrum of systems─lipid membranes, proteins (including peptides and amino acids), and saccharides─without compromising their biomolecular structures. prosECCo75 thus emerges as a computationally efficient tool providing enhanced accuracy and broader applicability in simulating the complex interplay of interactions between ions and biomolecules, pivotal for improving our understanding of many biological processes.

• MeSH
• Peptides chemistry   MeSH
• Proteins chemistry   MeSH
• Molecular Dynamics Simulation * MeSH
• Static Electricity * MeSH
• Water chemistry   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Peptides MeSH
• Proteins MeSH
• Water MeSH

Cholesterol is a central building block in biomembranes, where it induces orientational order, slows diffusion, renders the membrane stiffer, and drives domain formation. Molecular dynamics (MD) simulations have played a crucial role in resolving these effects at the molecular level; yet, it has recently become evident that different MD force fields predict quantitatively different behavior. Although easily neglected, identifying such limitations is increasingly important as the field rapidly progresses toward simulations of complex membranes mimicking the in vivo conditions: pertinent multicomponent simulations must capture accurately the interactions between their fundamental building blocks, such as phospholipids and cholesterol. Here, we define quantitative quality measures for simulations of binary lipid mixtures in membranes against the C-H bond order parameters and lateral diffusion coefficients from NMR spectroscopy as well as the form factors from X-ray scattering. Based on these measures, we perform a systematic evaluation of the ability of commonly used force fields to describe the structure and dynamics of binary mixtures of palmitoyloleoylphosphatidylcholine (POPC) and cholesterol. None of the tested force fields clearly outperforms the others across the tested properties and conditions. Still, the Slipids parameters provide the best overall performance in our tests, especially when dynamic properties are included in the evaluation. The quality evaluation metrics introduced in this work will, particularly, foster future force field development and refinement for multicomponent membranes using automated approaches.

• MeSH
• Cholesterol chemistry   MeSH
• Phosphatidylcholines * chemistry   MeSH
• Lipid Bilayers * chemistry   MeSH
• Molecular Dynamics Simulation MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 1-palmitoyl-2-oleoylphosphatidylcholine MeSH Browser
• Cholesterol MeSH
• Phosphatidylcholines * MeSH
• Lipid Bilayers * MeSH

In this work, the influence of membrane curvature on the Ca2+ binding to phospholipid bilayers is investigated by means of molecular dynamics simulations. In particular, we compared Ca2+ binding to flat, elastically buckled, or uniformly bent zwitterionic and anionic phospholipid bilayers. We demonstrate that Ca2+ ions bind preferably to the concave membrane surfaces in both types of bilayers. We also show that the membrane curvature leads to pronounced changes in Ca2+ binding including differences in free ion concentrations, lipid coordination distributions, and the patterns of ion binding to different chemical groups of lipids. Moreover, these effects differ substantially for the concave and convex membrane monolayers. Comparison between force fields with either full or scaled charges indicates that charge scaling results in reduction of the Ca2+ binding to curved phosphatidylserine bilayers, while for phosphatidylcholine membranes, calcium binds only weakly for both force fields.

• MeSH
• Phosphatidylcholines chemistry   MeSH
• Phospholipids * chemistry   MeSH
• Ions MeSH
• Lipid Bilayers * chemistry   MeSH
• Molecular Dynamics Simulation MeSH
• Calcium chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Phosphatidylcholines MeSH
• Phospholipids * MeSH
• Ions MeSH
• Lipid Bilayers * MeSH
• Calcium MeSH

Adsorption of arginine-rich positively charged peptides onto neutral zwitterionic phosphocholine (PC) bilayers is a key step in the translocation of those potent cell-penetrating peptides into the cell interior. In the past, we have shown both theoretically and experimentally that polyarginines adsorb to the neutral PC-supported lipid bilayers in contrast to polylysines. However, comparing our results with previous studies showed that the results often do not match even at the qualitative level. The adsorption of arginine-rich peptides onto 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) may qualitatively depend on the actual experimental conditions where binding experiments have been performed. In this work, we systematically studied the adsorption of R9 and K9 peptides onto the POPC bilayer, aided by molecular dynamics (MD) simulations and fluorescence cross-correlation spectroscopy (FCCS) experiments. Using MD simulations, we tested a series of increasing peptide concentrations, in parallel with increasing Na+ and Ca2+ salt concentrations, showing that the apparent strength of adsorption of R9 decreases upon the increase of peptide or salt concentration in the system. The key result from the simulations is that the salt concentrations used experimentally can alter the picture of peptide adsorption qualitatively. Using FCCS experiments with fluorescently labeled R9 and K9, we first demonstrated that the binding of R9 to POPC is tighter by almost 2 orders of magnitude compared to that of K9. Finally, upon the addition of an excess of either Na+ or Ca2+ ions with R9, the total fluorescence correlation signal is lost, which implies the unbinding of R9 from the PC bilayer, in agreement with our predictions from MD simulations.

• MeSH
• Adsorption MeSH
• Arginine MeSH
• Phosphatidylcholines chemistry   MeSH
• Phosphorylcholine MeSH
• Lecithins MeSH
• Lipid Bilayers * chemistry   MeSH
• Osmolar Concentration MeSH
• Cell-Penetrating Peptides * chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Arginine MeSH
• Phosphatidylcholines MeSH
• Phosphorylcholine MeSH
• Lecithins MeSH
• Lipid Bilayers * MeSH
• Cell-Penetrating Peptides * MeSH