Computer simulations of membrane proteins

Ash, Walter L.; Zlomislic, Marian R.; Oloo, Eliud O.; Tieleman, D. Peter

doi:10.1016/j.bbamem.2004.04.012

Cited by 233 publications

(165 citation statements)

References 322 publications

Supporting

Mentioning

162

Contrasting

Unclassified

Order By: Relevance

“…Due to these inherent experimental difficulties in obtaining structural data for membrane proteins, it is essential that we maximize our understanding of the structural/functional relationships of those membrane proteins for which we have experimental structures. Computational approaches have proven to be useful and have become a standard tool for investigations of membrane proteins [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Moreover, a combination of molecular modeling and simulation helps us to extrapolate from the structure of prokaryotic membrane proteins to the structure and dynamics of their human homologues, which may also aid in experimental structure determination.…”

Section: Membrane Proteinsmentioning

confidence: 99%

“…There have been a vast number of simulation studies of potassium channels since the first KcsA structure was published. Many of these studies have been reviewed several times in past years [11,14,15,20,23,35,[37][38][39][40][41]. This computational approach consists in monitoring the evolution in time of the system of interest where the interactions between atoms are described by simple empirical potential functions.…”

Section: Molecular Dynamic Simulations Of Ion Channelsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular dynamics simulations of potassium channels

Domene

2007

Open Chemistry

View full text Add to dashboard Cite

Despite the complexity of ion-channels, MD simulations based on realistic all-atom models have become a powerful technique for providing accurate descriptions of the structure and dynamics of these systems, complementing and reinforcing experimental work. Successful multidisciplinary collaborations, progress in the experimental determination of three-dimensional structures of membrane proteins together with new algorithms for molecular simulations and the increasing speed and availability of supercomputers, have made possible a considerable progress in this area of biophysics. This review aims at highlighting some of the work in the area of potassium channels and molecular dynamics simulations where numerous fundamental questions about the structure, function, folding and dynamics of these systems remain as yet unresolved challenges.

show abstract

Section: Membrane Proteinsmentioning

confidence: 99%

Section: Molecular Dynamic Simulations Of Ion Channelsmentioning

confidence: 99%

Molecular dynamics simulations of potassium channels

Domene

2007

Open Chemistry

View full text Add to dashboard Cite

show abstract

“…Several computational methods enable modeling of membrane proteins. 27,28 Coarse-grained (CG) simulations, in which sets of atoms are grouped together to one bead, allow faster computation and have been used to probe biologically relevant time and length scales. 16,23,29,30 These models were shown to be successful in predicting bulk material properties 31 as well as in describing molecular level phenomena.…”

Section: Introductionmentioning

confidence: 99%

Lipid mediated packing of transmembrane helices – a dissipative particle dynamics study

Benjamini

Smit

2013

Soft Matter

View full text Add to dashboard Cite

Interactions of transmembrane (TM) helices play a key role in many cell processes. The configuration and cross angle these helices adopt are traditionally attributed to specific residue interactions. We present a different approach, in which specific residues are disregarded, and the role of the membrane in TM helix packing is investigated. We introduce a coarse-grained model of TM helices and obtain their characteristic configurations in the membrane both as a single helix and as paired helices. Our analysis shows that hydrophobic mismatch has a substantial effect in determining not only the tilt angles of TM helices but also the cross angles between helix pairs, for a large range of hydrophobic mismatches. We discuss the origin of this effect as well as the deviations from the common trend. Additionally, we explore the effect of hydrophobic mismatch on the Potential of Mean Force (PMF) between TM helices and discuss the importance of helical geometry in forming crossed configurations. Our observations suggest that hydrophobic mismatch must be taken into account when analyzing configurations of TM helix pairs. Hydrophobic mismatch through its effect on helix tilt can explain many cross-angle distribution features, making the role of specific interactions in determining helix pair configurations less significant.

show abstract

“…The use of coarse-grain simulation has also been expanded to lipid bilayer self-assembly on several membrane proteins including E. coli TolC, which the authors propose can be used to predict the position of the protein in the membrane [20]. However, as the specific membrane environment could potentially modulate the behavior of some membrane proteins, full detailed atomistic simulation is preferable in many cases [64].…”

Section: Discussionmentioning

confidence: 99%

Assembly and stability of Salmonella enterica ser. Typhi TolC protein in POPE and DMPE

et al. 2014

View full text Add to dashboard Cite

In this work we assessed the suitability of two different lipid membranes for the simulation of a TolC protein from Salmonella enterica serovar Typhi. The TolC protein family is found in many pathogenic Gram-negative bacteria including Vibrio cholera and Pseudomonas aeruginosa and acts as an outer membrane channel for expulsion of drug and toxin from the cell. In S. typhi, the causative agent for typhoid fever, the TolC outer membrane protein is an antigen for the pathogen. The lipid environment is an important modulator of membrane protein structure and function. We evaluated the conformation of the TolC protein in the presence of DMPE and POPE bilayers using molecular dynamics simulation. The S. typhi TolC protein exhibited similar conformational dynamics to TolC and its homologues. Conformational flexibility of the protein is seen in the C-terminal, extracellular loops, and α-helical region. Despite differences in the two lipids, significant similarities in the motion of the protein in POPE and DMPE were observed, including the rotational motion of the C-terminal residues and the partially open extracellular loops. However, analysis of the trajectories demonstrated effects of hydrophobic matching of the TolC protein in the membrane, particularly in the lengthening of the lipids and subtle movements of the protein's β-barrel towards the lower leaflet in DMPE. The study exhibited the use of molecular dynamics simulation in revealing the differential effect of membrane proteins and lipids on each other. In this study, POPE is potentially a more suitable model for future simulation of the S. typhi TolC protein.

show abstract

Computer simulations of membrane proteins

Cited by 233 publications

References 322 publications

Molecular dynamics simulations of potassium channels

Molecular dynamics simulations of potassium channels

Lipid mediated packing of transmembrane helices – a dissipative particle dynamics study

Assembly and stability of Salmonella enterica ser. Typhi TolC protein in POPE and DMPE

Contact Info

Product

Resources

About