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Atomic-level description of protein-lipid interactions using an accelerated membrane model.

ABSTRACT: Peripheral membrane proteins are structurally diverse proteins that are involved in fundamental cellular processes. Their activity of these proteins is frequently modulated through their interaction with cellular membranes, and as a result techniques to study the interfacial interaction between peripheral proteins and the membrane are in high demand. Due to the fluid nature of the membrane and the reversibility of protein-membrane interactions, the experimental study of these systems remains a challenging task. Molecular dynamics simulations offer a suitable approach to study protein-lipid interactions; however, the slow dynamics of the lipids often prevents sufficient sampling of specific membrane-protein interactions in atomistic simulations. To increase lipid dynamics while preserving the atomistic detail of protein-lipid interactions, in the highly mobile membrane-mimetic (HMMM) model the membrane core is replaced by an organic solvent, while short-tailed lipids provide a nearly complete representation of natural lipids at the organic solvent/water interface. Here, we present a brief introduction and a summary of recent applications of the HMMM to study different membrane proteins, complementing the experimental characterization of the presented systems, and we offer a perspective of future applications of the HMMM to study other classes of membrane proteins. This article is part of a Special Issue entitled: Membrane proteins edited by J.C. Gumbart and Sergei Noskov.

SUBMITTER: Baylon JL

PROVIDER: S-EPMC4877275 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Atomic-level description of protein-lipid interactions using an accelerated membrane model.

Baylon Javier L JL Vermaas Josh V JV Muller Melanie P MP Arcario Mark J MJ Pogorelov Taras V TV Tajkhorshid Emad E

Biochimica et biophysica acta 20160302 7 Pt B

Peripheral membrane proteins are structurally diverse proteins that are involved in fundamental cellular processes. Their activity of these proteins is frequently modulated through their interaction with cellular membranes, and as a result techniques to study the interfacial interaction between peripheral proteins and the membrane are in high demand. Due to the fluid nature of the membrane and the reversibility of protein-membrane interactions, the experimental study of these systems remains a c ...[more]

PMID: 26940626

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Project description:BackgroundShape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes.Methodology and principal findingsWe show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites.Conclusions and significanceWe show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.

Project description:Adsorption of synthetic alanine-rich peptides to lipid monolayers was studied by X-ray and neutron reflectivity, grazing incidence X-ray diffraction (GIXD), and circular dichroic spectroscopy. The peptides contained histidine residues to drive adsorption to Langmuir monolayers of lipids with iminodiacetate headgroups loaded with Cu2+. Adsorption was found to be irreversible with respect to bulk peptide concentration. The peptides were partially helical in solution at room temperature, the temperature of the adsorption assays. Comparisons of the rate of binding and the structure of the adsorbed layer were made as a function of the number of histidines (from 0 to 2) and also as a function of the positioning of the histidines along the backbone. For peptides containing two histidines on the same side of the helical backbone, large differences were observed in the structure of the adsorbed layer as a function of the spacing of the histidines. With a spacing of 6 A, there was a substantial increase in helicity upon binding (from 17% to 31%), and the peptides adsorbed to a final density approaching that of a nearly completed monolayer of alpha-helices adsorbed side-on. The thickness of the adsorbed layer (17 +/- 2.5 A) was slightly greater than the diameter of alpha-helices, suggesting that the free, unstructured ends extended into solution. With a spacing of 30 A between histidines, a far weaker increase in helicity upon binding was observed (from 13% to 19%) and a much lower packing density resulted. The thickness of the adsorbed layer (10 +/- 4 A) was smaller, consistent with the ends being bound to the monolayer. Striking differences were observed in the interaction of the two types of peptide with the lipid membrane by GIXD, consistent with binding by two correlated sites only for the case of 6 A spacing. All these results are attributed to differences in spatial correlation between the histidines as a function of separation distance along the backbone for these partially helical peptides. Finally, control over orientation was demonstrated by placing a histidine on an end of the sequence, which resulted in adsorbed peptides oriented perpendicular to the membrane.

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Atomic-level description of protein-lipid interactions using an accelerated membrane model.

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Atomic-level description of protein-lipid interactions using an accelerated membrane model.

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