Wyniki wyszukiwania - Biblioteka Nauki

1

Badania układów błonowych metodami modelowania molekularnego

100%

Pasenkiewicz-Gierula M.

|

nr 1-2

49-56

EN

Biological membranes enclose every cell (plasma membrane) and some intracellular organelles (internal membranes). The main structural element of a biological membrane is a liquid-crystalline lipid bilayer. Experimental studies of lipid bilayers are difficult to carry out and to interpret because of their structural disorder and superposition of motions occurring in different time scales. Besides, due to limited spatial and time resolutions, they provide only an averaged behaviour of the molecules in the bilayer. Detailed information about the dynamical structure and time scales of events in the membrane can be obtained using molecular dynamics (MD) simulation methods. Although MD simulation is, in principle, characterized by an atomic resolution and time resolution in the femtosecond time scale in principle, the total simulation time is limited at present to several hundred nanoseconds. So, the method allows observation of the processes up to the 10-7 s time scale. MD simulation studies of hydrated lipid bilayers have shown that at the membrane/water interface there are numerous but short-lived hydrogen (H-) bonds between lipid headgroups and water molecules as well as an extended network of interlipid links via water molecules that are simultaneously H-bonded to two lipid molecules, i.e., so called water bridges. Exchange of H2O by D2O affects the time-averaged properties of the PC bilayer to some extent. When the bilayer is hydrated by D2O it becomes more compact than in the case of H2O. This can be assigned to the more stable H-bonds between PC and D2O than H2O and, particularly, to the more stable network of D2O water bridges compared with the H2O ones. In effect, the self-diffusion coefficient of D2O averaged over all water molecules in the bilayer is almost twice smaller than that of H2O and ∼2.5 times smaller than in pure D2O (∼1.7 in the case of H2O).

2

Conformations, orientations and time scales characterising dimyristoylphosphatidylcholine bilayer membrane. Molecular dynamicssimulation studies

63%

Pasenkiewicz-Gierula M. , Róg T.

|

1997

|

tom 44

|

nr 3

607-624

3

The effect of the Glu342Lys mutation in α1-antitrypsin on its structure, studied by molecular modelling methods.

63%

Jezierski G. , Pasenkiewicz-Gierula M.

|

tom 48

|

nr 1

65-75

EN

The structure of native α1-antitrypsin, the most abundant protease inhibitor in human plasma, is characterised primarily by a reactive loop containing the centre of proteinase inhibition, and a β-sheet composed of five strands. Mobility of the reactive loop is confined as a result of electrostatic interactions between side chains of Glu342 and Lys290, both located at the junction of the reactive loop and the β structure. The most common mutation in the protein, resulting in its inactivation, is Glu342→Lys, named the Z mutation. The main goal of this work was to investigate the influence of the Z mutation on the structure of α1-antitrypsin. Commonly used molecular modelling methods have been applied in a comparative study of two protein models: the wild type and the Z mutant. The results indicate that the Z mutation introduces local instabilities in the region of the reactive loop. Moreover, even parts of the protein located far apart from the mutation region are affected. The Z mutation causes a relative change in the total energy of about 3%. Relatively small root mean square differences between the optimised structures of the wild type and the Z mutant, together with detailed analysis of 'conformational searching' process, lead to the hypothesis that the Z mutation principally induces a change in the dynamics of α1-antitrypsin.

4

Molecular dynamics simulation studies of lipid bilayer systems.

51%

Pasenkiewicz-Gierula M. , Murzyn K. , Róg T. , Czaplewski C.

|

nr 3

601-611

EN

The main structural element of biological membranes is a liquid-crystalline lipid bilayer. Other constituents, i.e. proteins, sterols and peptides, either intercalate into or loosely attach to the bilayer. We applied a molecular dynamics simulation method to study membrane systems at various levels of compositional complexity. The studies were started from simple lipid bilayers containing a single type phosphatidylcholine (PC) and water molecules (PC bilayers). As a next step, cholesterol (Chol) molecules were introduced to the PC bilayers (PC-Chol bilayers). These studies provided detailed information about the structure and dynamics of the membrane/water interface and the hydrocarbon chain region in bilayers built of various types of PCs and Chol. This enabled studies of membrane systems of higher complexity. They included the investigation of an integral membrane protein in its natural environment of a PC bilayer, and the antibacterial activity of magainin-2. The latter study required the construction of a model bacterial membrane which consisted of two types of phospholipids and counter ions. Whenever published experimental data were available, the results of the simulations were compared with them.