charmm2gmx: An Automated Method to Port the CHARMM Additive Force Field to GROMACS

CHARMM is one of the most widely used biomolecular force fields. Although developed in close connection with a dedicated molecular simulation engine of the same name, it is also usable with other codes. GROMACS is a well-established, highly optimized, and multipurpose software for molecular dynamics, versatile enough to accommodate many different force field potential functions and the associated algorithms. Due to conceptional differences related to software design and the large amount of numeric data inherent to residue topologies and parameter sets, conversion from one software format to another is not straightforward. Here, we present an automated and validated means to port the CHARMM force field to a format read by the GROMACS engine, harmonizing the different capabilities of the two codes in a self-documenting and reproducible way with a bare minimum of user interaction required. Being based entirely on the upstream data files, the presented approach does not involve any hard-coded data, in contrast with previous attempts to solve the same problem. The heuristic approach used for perceiving the local internal geometry is directly applicable for analogous transformations of other force fields

A mechanistic view of lipid membrane disrupting effect of PAMAM dendrimers

The effect of 5th generation polyamidoamine (PAMAM G5) dendrimers on multilamellar dipalmitoylphosphocholine (DPPC) vesicles was investigated. PAMAM was added in two different concentration to the lipids (10-3 and 10-2 dendrimer/lipid molar ratios). The thermal behavior of the evolved systems was characterized by DSC; while the structure and the morphology were investigated with small- and wide-angel X-ray scattering (SWAXS), freeze-fracture electron microscopy (FFTEM) and phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy, respectively. IR spectroscopy was used to study the molecular interactions between PAMAM and DPPC. The obtained results show that the dendrimers added in 10-3 molar ratio to the lipids generate minor perturbations in the multilamellar structure and thermal character of liposomes, while added in 10-2 molar ratio dendrimers cause major disturbance in the vesicular system. The terminal amino groups of the dendrimers are in strong interaction with the phosphate headgroups and through this binding dendrimers disrupt the regular multilamellar structure of DPPC. Besides highly swollen, fragmented bilayers, small vesicles are formed

Comparative Study of Molecular Mechanics Force Fields for β-Peptidic Foldamers: Folding and Self-Association

Computer-assisted study and design of non-natural peptidomimetics is increasingly important in the development of novel constructs with widespread applicability. Among these methods, molecular dynamics can accurately describe monomeric as well as oligomeric states of these compounds. We studied seven different sequences composed of cyclic and acyclic β-amino acids, the closest homologues of natural peptides, and compared the performance on them of three force field families in which specific modifications were made to improve reproduction of β-peptide structures. Altogether 17 systems were simulated, each for 500 ns, testing multiple starting conformations and in three cases also oligomer formation and stability from eight β-peptide monomers. The results indicated that our recently developed CHARMM force field extension, based on torsional energy path matching of the β-peptide backbone against quantum-chemical calculations, performs best overall, reproducing the experimental structures accurately in all monomeric simulations and correctly describing all the oligomeric examples. The Amber and GROMOS force fields could only treat some of the seven peptides (four in each case) without further parametrization. Amber was able to reproduce the experimental secondary structure of those β-peptides which contained cyclic β-amino acids, while the GROMOS force field had the lowest performance in this sense. From the latter two, Amber was able to hold together already formed associates in the prepared state but was not able to yield spontaneous oligomer formation in the simulations

Comparative Study of Molecular Mechanics Force Fields for β-Peptidic Foldamers: Folding and Self-Association

Computer-assisted study and design of non-natural peptidomimetics is increasingly important in the development of novel constructs with widespread applicability. Among these methods, molecular dynamics can accurately describe monomeric as well as oligomeric states of these compounds. We studied seven different sequences composed of cyclic and acyclic β-amino acids, the closest homologues of natural peptides, and compared the performance on them of three force field families in which specific modifications were made to improve reproduction of β-peptide structures. Altogether 17 systems were simulated, each for 500 ns, testing multiple starting conformations and in three cases also oligomer formation and stability from eight β-peptide monomers. The results indicated that our recently developed CHARMM force field extension, based on torsional energy path matching of the β-peptide backbone against quantum-chemical calculations, performs best overall, reproducing the experimental structures accurately in all monomeric simulations and correctly describing all the oligomeric examples. The Amber and GROMOS force fields could only treat some of the seven peptides (four in each case) without further parametrization. Amber was able to reproduce the experimental secondary structure of those β-peptides which contained cyclic β-amino acids, while the GROMOS force field had the lowest performance in this sense. From the latter two, Amber was able to hold together already formed associates in the prepared state but was not able to yield spontaneous oligomer formation in the simulations

Synthesis of poly(methyl methacrylate)-poly(poly(ethylene glycol) methacrylate)-polyisobutylene ABCBA pentablock copolymers by combining quasiliving carbocationic and atom transfer radical polymerizations and characterization thereof

Novel, unique amphiphilic pentab lock terpolymers consisting of the highly hydrophobic polyisobutylene (PIB) mid - segment attached to the hydrophilic combshaped poly(poly(ethylene glycol ) methacrylate) (PPEGMA) polymacromonomer chains, which are coupled to poly(methyl methacrylate) (PMMA) outer segments were synthesized by the combination of quasiliving carbocationic polymerization and atom transfer radical polymerization ( ATRP ) . First, a bifunctional PIB macroinitiator w as prepared by quasiliving carbocationic polymerization and subsequent quantitative chain end derivatizations. ATRP of PEGMAs with different molecular weights (M n = 188, 300 and 475 g/mol) led to triblock copolymers which were further reacted with MMA under ATRP conditions to obtain P MMA - PPE G MA - PIB - PPEGMA - PMMA AB CB A - type pen ta block copolymers . It was found that slow initi ation takes place between the PIB macroinitiator and PEGMA macromonomers with higher molecular weights via ATRP . ATRP of MMA with the resulting block copolymers composed of PIB and PPEGMA chain segments led t o the desired block copolymers with high initiating efficiency. Investigations of the resulting pentablock copolymers by DSC, SAXS and phase mode AFM revealed that nanophase separation occurs in these new macromolecular structures with average domain dista nces of 11 - 14 nm, and local lamellar self - assembly takes place in the pentablocks with PPEGMA polymacromonomer segments of PEGMAs with M n of 118 g/mol and 300 g/mol , while disordered nanophases are observed in the block copolymer with PEGMA having molecula r weight of 475 g/mol. These new amphiphilic block copolymers composed of biocompatible chain segments can find applications in a variety of advanced fields

Physicochemical characterization of artificial nanoerythrosomes derived from erythrocyte ghost membranes

Colloidal stabile nanoerythrosomes with 200 nm average diameter were formed from hemoglobin-free erythrocyte ghost membrane via sonication and membrane extrusion. The incorporation of extra lipid (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC), added to the sonicated ghosts, caused significant changes in the thermotropic character of the original membranes. As a result of the increased DPPC ratio the chain melting of the hydrated DPPC system and the characteristic small angle X-ray scattering (SAXS) of the lipid bilayers appeared. Significant morphological changes were followed by transmission electron microscopy combined with freeze fracture method (FF-TEM). After the ultrasonic treatment the large entities of erythrocyte ghosts transformed into nearly spherical nanoerythrosomes with diameters between 100 and 300 nm and at the same time a great number of 10–30 nm large membrane proteins or protein clusters were dispersed in the aqueous medium. The infrared spectroscopy (FT-IR) pointed out, that the sonication did not cause changes in the secondary structures of the membrane proteins under our preparation conditions. About fivefold of extra lipid – compared to the lipid content of the original membrane – caused homogeneous dispersion of nanoerythrosomes however the shape of the vesicles was not uniform. After the addition of about tenfold of DPPC, monoform and monodisperse nanoerythrosomes became typical. The outer surfaces of these roughly spherical objects were frequently polygonal, consisting of a net of pentagons and hexagons

Lipid Polymorphism of the Subchloroplast—Granum and Stroma Thylakoid Membrane–Particles. II. Structure and Functions

In Part I, by using P-31-NMR spectroscopy, we have shown that isolated granum and stroma thylakoid membranes (TMs), in addition to the bilayer, display two isotropic phases and an inverted hexagonal (H-II) phase; saturation transfer experiments and selective effects of lipase and thermal treatments have shown that these phases arise from distinct, yet interconnectable structural entities. To obtain information on the functional roles and origin of the different lipid phases, here we performed spectroscopic measurements and inspected the ultrastructure of these TM fragments. Circular dichroism, 77 K fluorescence emission spectroscopy, and variable chlorophyll-a fluorescence measurements revealed only minor lipase- or thermally induced changes in the photosynthetic machinery. Electrochromic absorbance transients showed that the TM fragments were re-sealed, and the vesicles largely retained their impermeabilities after lipase treatments-in line with the low susceptibility of the bilayer against the same treatment, as reflected by our P-31-NMR spectroscopy. Signatures of H-II-phase could not be discerned with small-angle X-ray scattering-but traces of H-II structures, without long-range order, were found by freeze-fracture electron microscopy (FF-EM) and cryo-electron tomography (CET). EM and CET images also revealed the presence of small vesicles and fusion of membrane particles, which might account for one of the isotropic phases. Interaction of VDE (violaxanthin de-epoxidase, detected by Western blot technique in both membrane fragments) with TM lipids might account for the other isotropic phase. In general, non-bilayer lipids are proposed to play role in the self-assembly of the highly organized yet dynamic TM network in chloroplasts

Lipid nanoparticles with erythrocyte cell-membrane proteins

When the separated erythrocyte membranes (known as ghosts) are ultrasonicated, a significant part of the membrane proteins are released in the aqueous solvent, instead of being incorporated into the membranes of the formed nanoerythrosomes. In contrast to their membrane-bound counterparts, where helices and β-strands dominate, the released proteins show perturbed secondary structures with an increased ratio of helices, presumably participating in molten globules, as it has been revealed by circular dichroism (CD) and infra-red spectroscopy (IR). The shape and size of these proteins is diverse, and even their aggregates appear. When excess lipid (palmitoyl-lysophosphatidylcholine, LPC) is added to different ghost-derivatives (the full nanoerythrosome system, and its ultracentrifugation pellet and supernatant) in 2 × and 5 × lipid-to-protein mass ratio, various lipid nanoparticles are produced. The core–shell and nanodisc structural models obtained by small-angle X-ray scattering (SAXS) indicate that the choice of the precursor system has a more prominent effect on the resulting shape than the amount of lipid added: when starting from the protein-rich supernatant fraction, small (approx. 5 nm high and 7 nm wide) nanodisks are created. When lipid membranes are already present (in the pellet and the full nanoerythrosome fraction), similar LPC addition results in prolate ellipsoidal particles, with an aspect ratio between 3 and 5, and decreasing overall size when the amount of added lipid is increased. The ellipsoids formed from the total nanoerythrosome fraction are smaller than those from the ultracentrifugation pellet (longest axis around 15 vs 26 nm), whereas for higher LPC-to-protein ratio, the size in both cases reduce to nearly the same (13–14 nm) in both cases