scholarly journals Computational studies of peptide-induced membrane pore formation

2017 ◽  
Vol 372 (1726) ◽  
pp. 20160219 ◽  
Author(s):  
Richard Lipkin ◽  
Themis Lazaridis
Keyword(s):  
Pore Formation ◽  
Coarse Grained ◽  
Future Research ◽  
Implicit Solvent ◽  
Computational Studies ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Solvent Models ◽  
Future Research Directions ◽  
Implicit Solvent Models

A variety of peptides induce pores in biological membranes; the most common ones are naturally produced antimicrobial peptides (AMPs), which are small, usually cationic, and defend diverse organisms against biological threats. Because it is not possible to observe these pores directly on a molecular scale, the structure of AMP-induced pores and the exact sequence of steps leading to their formation remain uncertain. Hence, these questions have been investigated via molecular modelling. In this article, we review computational studies of AMP pore formation using all-atom, coarse-grained, and implicit solvent models; evaluate the results obtained and suggest future research directions to further elucidate the pore formation mechanism of AMPs. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.

Transferability of Coarse Grained Potentials: Implicit Solvent Models for Hydrated Ions

2011 ◽  
Vol 7 (6) ◽  
pp. 1916-1927 ◽  
Author(s):  
Jia-Wei Shen ◽  
Chunli Li ◽  
Nico F.A. van der Vegt ◽  
Christine Peter
Keyword(s):  
Coarse Grained ◽  
Implicit Solvent ◽  
Hydrated Ions ◽  
Solvent Models ◽  
Implicit Solvent Models

scholarly journals Membrane perforation by the pore-forming toxin pneumolysin

2019 ◽  
Vol 116 (27) ◽  
pp. 13352-13357 ◽  
Author(s):  
Martin Vögele ◽  
Ramachandra M. Bhaskara ◽  
Estefania Mulvihill ◽  
Katharina van Pee ◽  
Özkan Yildiz ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Pore Formation ◽  
Line Tension ◽  
Coarse Grained ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Membrane Perforation ◽  
Membrane Spanning ◽  
Dynamics Simulations ◽  
Key Steps

Pneumolysin (PLY), a major virulence factor ofStreptococcus pneumoniae, perforates cholesterol-rich lipid membranes. PLY protomers oligomerize as rings on the membrane and then undergo a structural transition that triggers the formation of membrane pores. Structures of PLY rings in prepore and pore conformations define the beginning and end of this transition, but the detailed mechanism of pore formation remains unclear. With atomistic and coarse-grained molecular dynamics simulations, we resolve key steps during PLY pore formation. Our simulations confirm critical PLY membrane-binding sites identified previously by mutagenesis. The transmembrane β-hairpins of the PLY pore conformation are stable only for oligomers, forming a curtain-like membrane-spanning β-sheet. Its hydrophilic inner face draws water into the protein–lipid interface, forcing lipids to recede. For PLY rings, this zone of lipid clearance expands into a cylindrical membrane pore. The lipid plug caught inside the PLY ring can escape by lipid efflux via the lower leaflet. If this path is too slow or blocked, the pore opens by membrane buckling, driven by the line tension acting on the detached rim of the lipid plug. Interestingly, PLY rings are just wide enough for the plug to buckle spontaneously in mammalian membranes. In a survey of electron cryo-microscopy (cryo-EM) and atomic force microscopy images, we identify key intermediates along both the efflux and buckling pathways to pore formation, as seen in the simulations.

scholarly journals The validation of quantum chemical lipophilicity prediction of alcohols

2016 ◽  
Vol 9 (2) ◽  
pp. 89-94 ◽  
Author(s):  
Martin Michalík ◽  
Vladimír Lukeš
Keyword(s):  
Linear Correlation ◽  
Quantum Chemical ◽  
Partition Coefficients ◽  
The Other ◽  
Basis Set ◽  
Implicit Solvent ◽  
Solvent Models ◽  
Lipophilicity Prediction ◽  
Triple Zeta ◽  
Implicit Solvent Models

AbstractThe validation of octanol-water partition coefficients (logP) quantum chemical calculations is presented for 27 alkane alcohols. The chemical accuracy of predicted logPvalues was estimated for six DFT functionals (B3LYP, PBE0, M06-2X, ωB97X-D, B97-D3, M11) and three implicit solvent models. Triple-zeta basis set 6-311++G(d,p) was employed. The best linear correlation with the experimental logPvalues was achieved for the B3LYP and B97-D3 functionals combined with the SMD model. On the other hand, no linearity was found when IEF-PCM or C-PCM implicit models were employed.

Generalized Born implicit solvent models for small molecule hydration free energies

2017 ◽  
Vol 19 (2) ◽  
pp. 1677-1685 ◽  
Author(s):  
Martin Brieg ◽  
Julia Setzler ◽  
Steffen Albert ◽  
Wolfgang Wenzel
Keyword(s):  
Free Energy ◽  
Small Molecules ◽  
Implicit Solvent ◽  
Free Energies ◽  
Hydration Free Energy ◽  
Energy Estimation ◽  
Generalized Born ◽  
Solvent Models ◽  
Molecular Force ◽  
Implicit Solvent Models

Hydration free energy estimation of small molecules from all-atom simulations was widely investigated in recent years, as it provides an essential test of molecular force fields and our understanding of solvation effects.

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