Wyniki wyszukiwania - BazTech

1

Influence of substitutions of Isu1 residues on binding to Jac1 protein

Mozolewska M. A.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

|

2016

|

Vol. 20, No 4

417--424

EN

The iron-sulfur (Fe/S) clusters are the most ancient co-factors of proteins involved in the most essential processes in bacterial systems and yeast, such as Saccharomyces cerevisiae. The main protein involved in the Fe/S cluster transfer is the Iron sulfur cluster assembly protein 1 (Isu1), which interacts with Jac1 during one of the stages of the Fe/S cluster biogenesis cycle forming a binary complex. In this work, the interaction interface of Isu1 was investigated by selective substitutions of amino-acid residues to understand their role in binding to the Jac1 protein. An initial alanine scan was done to limit the number of possible residues subjected to the replacement and to confirm the previously obtained results. Then, MD simulations using the coarse-grained UNRES force field were run for two selected mutants: L63 V72 F94 and L63 V64 G65 D71. The analysis of the dynamics and interaction patterns of the Isu1-Jac1 complexes confirmed that the investigated residues played an important role in their binding.

2

Towards mechanisms of nanotoxicity - interaction of gold nanoparticles with proteins and DNA

Krupa P., Mozolewska M. A., Rasulev B., Czaplewski C., Leszczyński J.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

|

2014

|

Vol. 18, No 4

337--341

EN

Even though most of the existing studies of gold nanoparticles indicate that they are safe to use, some researchers show that specific forms of nanoparticles (e.g. nanorods) are able to destroy the cell membrane and very small nanoparticles (below 37nm in diameter) in high concentration have been deadly for mice. We used the Amber12 package to perform a series of molecular dynamics (MD) simulations of gold nanoparticles with various small proteins important for the human body and a DNA molecule to determine the interactions and consequently the possible toxicity of gold clusters. Lennard-Jones interactions were used to simulate the behavior of gold nanoparticles with biomacromolecules in water with an optimal set of parameters (selected based on a comparison of MD structures and structures computed by DFT). Gold nanoparticle structures were obtained as a result of MD simulations from an initial structure, where gold atoms were at a distance of 10 ̊ A from one another. A predicted BDNA structure of a palindromic sequence‘ CGCATGAGTACGC ’ and a 2 JYK molecule were used as representatives of the DNA molecule. The preliminary results show that, in particular small gold nanoparticle s, interact strongly with proteins and DNA by creating stable complexes, which can then cause harmful reactions to the human body when present in high concentration.

3

Preliminary studies of interaction between nanotubes and toll-like receptors

Mozolewska M. A., Krupa P., Rasulev B., Liwo A., Leszczyński J.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

|

2014

|

Vol. 18, No 4

351--355

EN

Toll-like receptors ( TLR s) are a group of proteins which play a crucial role in the innate immune system. The main function of TLR s is to recognize structurally conserved molecules, which are inserted to the organism of the host by microbes, and then to activate the immune response. Current development of drugs is often connected not only with the drug itself, but also with the way it is delivered into the human body to interact direc tly with the source of the problem. Carbon nanostructures, particularly nanotubes, are one of the car rier molecules of the future. However, there is still no knowledge about the exact mechani sms of toxicity and possible interactions with macromolecules, such as proteins. In our study we tr ied to determine, if the nanotubes could interfere with the innate immune system by interac ting with TLR s. For this purpose, we used the following TLR structures downloaded from the RCSB Protein Data Bank: TLR 2 (3 A 7 C ), TLR 4/ MD (3 FXI ), TLR 5 (3 V 47), TLR 3 (2 A 0 Z ), and the complexes of TLR 1/ TLR 2 (2 Z 7 X ) and TLR 2/ TLR 6 (3 A 79). The preliminary results of our Steered Molecular Dynamics ( SMD ) simulations have shown that nanotubes interact very strongly with the binding pockets of some receptors ( e.g. TLR 2), which results in their binding to these sites without subst antial use of the external force.