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O Edholm

Publications and source records attributed to O Edholm.

12 recordsLinked to original sources
PubMed1995

Structure and fluctuations of bacteriorhodopsin in the purple membrane: a molecular dynamics study.

Molecular dynamics simulations on bacteriorhodopsin were performed starting from the model structure described by Henderson et al. The simulations were gradually improved by first treating a monomer in vacuum and then adding further monomers, lipids, and water to finally simulate a unit cell of the hexagonal lattice of the purple membrane containing a trimer and lipids and water on both sides. During all simulations, the protein structure moved away from the model structure to reach a root-mean-square (r.m.s.) deviation of 2 to 3 A. In the simulations with the trimer, the structures of the three monomers differed by about the same amount and averaging over them led to an average structure with a considerably smaller r.m.s. deviation. The best average structure obtained had an r.m.s. deviation from the model structure of 1.3 A. Fluctuations of the protein, the lipids, and water were analyzed in detail. As expected, the membrane-spanning helices of the protein fluctuate less than the peripheral loops. Unexpected, however, was the finding that the fluctuations of the protein are asymmetric with respect to the midplane of the membrane. The fluctuations of the loops and the ends of the helices on the inner side of the membrane are much stronger than on the outer side. This asymmetry is also reflected by the fluctuations for the lipids, the lipids of the inner leaflet fluctuating more strongly than those of the outer leaflet. The asymmetry was observed only in the presence of water on both sides of the membrane. On the average, nine water molecules were found inside the protein, most of them undergoing exchange with external water.

Amino Acid Sequence↗
PubMed1994

Molecular dynamics study of the binding of phenylalanine stereoisomers to thermolysin.

The stereospecificity in binding of phenylalanine as inhibitor in the active site of the thermolysin, has been investigated by means of molecular dynamics simulations using free energy integration techniques. The difference in the free energy of binding was found to be 2.0 +/- 1.8 kJ/mol in favour of the D-form. This agrees with the experimental value, 2.8 kJ/mol. The result was obtained using a standard empirical force field (that of GROMOS). A different force field with 30% bigger charges (more like ab initio charges) was also tried. This resulted in less fluctuations and a more precise binding, but in a free energy difference that was clearly larger than the experimental one. The phenylalanine backbone is located close to the zinc atom and the ring stays in the hydrophobic pocket in both the cases. The two stereoisomers differ mainly in the orientation of the backbone plane with respect to the active site and the rotational state of the dihedral around the C alpha-C beta bond.

Binding Sites↗
PubMed1994

Molecular dynamics simulations of an enzyme surrounded by vacuum, water, or a hydrophobic solvent.

We report on molecular dynamics simulations of a medium-sized protein, a lipase from Rhizomucor miehei, in vacuum, in water, and in a nonpolar solvent, methyl hexanoate. Depending on force field and solvent, the molecular dynamics structures obtained as averages over 150 ps had root-mean-square deviations in the range of 1.9 to 3.6 A from the crystal structure. The largest differences between the structures were in hydrogen bonding and exposed surface areas of the protein. The surface area increased in both solvents and became smaller in vacuum. The change of surface exposure varied greatly between different residues and occurred in accordance with the hydrophobicity of the residue and the nature of the solvent. The fluctuations of the atoms were largest in the external loops and agreed well with crystallographic temperature factors. Root-mean-square fluctuations were significantly smaller in the nonpolar solvents than they were in water, which is in accordance with the notion that proteins become more rigid in nonpolar solvents. In methyl hexanoate a partial opening of the lid covering the active site occurred, letting a methyl hexanoate molecule approach the active site.

Computer Simulation↗
PubMed1993

Theoretical studies of Rhizomucor miehei lipase activation.

Computational methods have been used to study the extensive conformational change of Rhizomucor miehei lipase upon activation. The present study considers the possible activation route, the energies involved and molecular interactions during the conformational change of the lipase in a hydrophobic environment. The conformational change was studied by conventional molecular dynamics methods and with a combined molecular dynamics and mechanics protocol, in which the conformational change was simulated by restraining C alpha pseudotorsional angles in small steps between the two crystallographically observed positions of the lid. In the closed conformer of the enzyme the active site is completely buried under a short helical loop, 'the lid'. The activation of the lipase consists of a movement of the lid, which results in an open conformer with an exposed active site. From the results of the simulations in the present work we suggest that the lipase in a hydrophobic environment is stabilized in the open form by electrostatic interactions.

Computer Simulation↗
PubMed1992

Modeling of the structure of bacteriorhodopsin. A molecular dynamics study.

Secondary structure predictions for membrane proteins are relatively reliable and permit the construction of model structures that may serve as initial conformations for molecular dynamics simulations. This might provide a scheme to predict the three-dimensional structures of membrane proteins. The feasibility of such an approach is tested for bacteriorhodopsin. We were not able to fully predict the kidney-shaped structure of bacteriorhodopsin. However, features compatible with this structure developed in a simulation starting from a circular arrangement of the seven predicted helices. When instead we started from the kidney shape, assigning the seven predicted helices in different ways to those on the structure, we could distinguish between the different assignments on the basis of energy and tilt of the helices. In this way we could select the correct assignment from a few others. For the correct assignment, the helices spontaneously adopted a tilt that agrees remarkably well with the experimental model structure derived by others. The root-mean-square deviation between our best molecular dynamics structure and the experimental model structure is 3.8 A, caused mainly by deviations in the internal degrees of freedom of the helices.

Amino Acid Sequence↗
PubMed1992

Cholesterol in model membranes. A molecular dynamics simulation.

Molecular dynamics simulations of a model membrane with inserted cholesterol molecules have been performed to study the perturbing influence of cholesterol. In the fluid phase of a lipid bilayer at 13 mol% concentration of cholesterol, local ordering of the hydrocarbon chains is induced. This perturbation decays with the distance from the cholesterol, and the effect extends 1.25 nm. It can be monitored in several ways, e.g., by an order parameter corresponding to deuterium nuclear magnetic resonance quadrupolar splittings, by the fraction of gauche bonds, or by the local bilayer thickness. At constant surface density, the local ordering is accompanied by disordering of the bulk phase, and, consequently, the net ordering effect is small. After compressing the system laterally in accordance with experimentally known surface areas, the bulk order parameters agree with those of a pure system, and the average order parameters are in accordance with experimental data. The necessity for this lateral compression is supported by calculated lateral pressures. At lower cholesterol concentration (3%), no direct perturbing effect is observed. A smaller lateral pressure than in a pure system indicates that the system with cholesterol is expected to have a smaller surface area, which would result in an increase of the order parameters, thus accounting for the experimental observations. The lack of spatial variation is, however, puzzling and may indicate a cooperative ordering effect.

Cholesterol↗
PubMed1991

Conformation and aggregation of M13 coat protein studied by molecular dynamics.

Molecular dynamics (MD) simulations are performed on M13 coat protein, a small membrane protein for which both alpha- and beta-structures have been suggested. The simulations are started from initial conformations that are either monomers or dimers of alpha-helices or U-shaped beta-sheets. The lipid bilayer is represented by a hydrophobic potential. The results are analyzed in terms of stability, energy and secondary structure. The U-shaped beta-structure changes from a planar to a twisted form with larger twist for the monomer than the dimer. The beta-sheet is much more flexible than the alpha-helix as monitored by the root mean square (rms) fluctuations of the C alpha atoms. A comparison of the energies after 100 ps MD simulation shows that of the monomers, the alpha-helix has the lowest energy. The energy difference between alpha- and beta-structures decreases from 266 kJ/mol to 148 kJ/mol, when going from monomers to dimers. It is expected that this difference will decrease with higher aggregation numbers.

Amino Acid Sequence↗
PubMed1988

The structure of a membrane-spanning polypeptide studied by molecular dynamics.

We have performed a molecular dynamics simulation of a 46-residue segment of glycophorin which includes the hydrophobic membrane-spanning region of this protein. The presence of a membrane and of water is taken into account in a continuum approximation which makes use of phenomenological hydrophobic energies. The initial alpha-helical conformation and the membrane incorporation of the hydrophobic segment remain stable for the length of the simulation which is 100 ps. Moreover, when the hydrophobic segment is partially shifted out of the membrane, it moves back into the membrane. Superimposed on these deterministic effects one also observes thermal fluctuations in the form of bending and tilting of the membrane-spanning helix.

Amino Acid Sequence↗
PubMed1987

Lipid bilayer polypeptide interactions studied by molecular dynamics simulation.

A model membrane with a polypeptide alpha-helix inserted has been simulated by molecular dynamics at a temperature well above the gel/liquid crystalline phase transition temperature. Order parameters of the lipids and other equilibrium and dynamic quantities have been calculated. Three systems, polyglycine constrained into an alpha-helical configuration, glycophorin with similarly conformationally constrained backbone and finally glycophorin free to change its backbone conformation, have been studied. In all cases there was an ordering of the chains close to the helix. This effect was, however, much smaller for glycophorin with its rather bulky side chains than for polyglycine. The dynamics of the lipids were affected by the neighbouring helix, not drastically however. Lateral diffusion and reorientational time correlations of lipids close to the helix were slower than for the bulk ones, but not more than two or three times. Thus, we did not find any evidence of bound or frozen boundary lipids.

Glycophorins↗
PubMed1979

Orienting responses and locus of control.

Few studies have attempted to relate the locus of control (Rotter, 1966) variable to physiological activity. This paper describes the heart-rate and skin conductance responses of 40 subjects exposed to a series of auditory stimuli, in relation to their locus of control scores. It was found that those scoring relatively 'externally' on the locus of control scale gave less decelerative and more accelerative heart-rate responses and tended to give larger skin conductance responses when there was a change in stimulus characteristics, than those scoring 'internally'. These results may be interpreted to support Lazarus' (1966) suggestions that control over a situation lessens the threat perceived in that situation. They also indicate that internal subjects tend to seek information to increase their control.

Adult↗