Marta Kulik

University of Warsaw | UW · Biological and Chemical Research Centre Faculty of Chemistry

Electrostatic interactions often play key roles in the recognition of small molecules by nucleic acids. An example is aminoglycoside antibiotics, which by binding to ribosomal RNA (rRNA) affect bacterial protein synthesis. These antibiotics remain one of the few valid treatments against hospital-acquired infections by Gram-negative bacteria. It is...

A corrected and improved structure of the polymorph II of 2C3H8NO3 +·C2O4 2−·2H2O, based on single-crystal data, is presented. The structure is refined with anisotropic displacement parameters for all non-H atoms and all H atoms are located. Due to the charged moieties, the structure is classified as a mol­ecular salt. Inter­molecular O—H⋯O−, O—H⋯O...

Electrostatic energy has a significant contribution to intermolecular interaction energy, especially in biological systems. Unfortunately, precise quantum mechanics calculations are not feasible for large biological systems; hence, simpler calculation methods are required. We propose a method called UBDB+EPMM (University at Buffalo Pseudoatom DataB...

In the simplest approach and at low resolution, the electron density of an atom can be approximated by a sphere. However, the resolutions currently achieved in X-ray crystallography reach near-atomic and atomic resolutions, where a more sophisticated approach is necessary. This review summarizes the available electron density and scattering factor...

The multipole model (MM) uses an aspherical approach to describe electron density and can be used to interpret data from X-ray diffraction in a more accurate manner than using the spherical approximation. The MATTS (multipolar atom types from theory and statistical clustering) data bank gathers MM parameters specific for atom types in proteins, nuc...

The availability of atomic resolution experimental maps of electrostatic potential from 3D electron diffraction (3D ED) extends the possibility of investigating the electrostatic potential beyond the determination of non-H-atom positions. However, accurate tools to calculate this potential for macromolecules, without the use of expensive quantum ca...

The SARS-CoV-2 virus has now become one of the greatest causes of infectious death and morbidity since the 1918 flu pandemic. Substantial and unprecedented progress has been made in the elucidation of the viral infection process in a short time; however, our understanding of the structure–function dynamics of the spike protein during the membrane f...

Structure determination using cryo-electron microscopy (cryo-EM) medium-resolution density maps is often facilitated by flexible fitting. Avoiding overfitting, adjusting force constants driving the structure to the density map, and emulating complex conformational transitions are major concerns in the fitting. To address them, we develop a new meth...

Short, structured fragments of non-coding mRNA may act as molecular switches upon binding specific ligands, regulating the translation of proteins encoded downstream this mRNA sequence. One switch, called riboswitch N1, is regulated by aminoglycosides such as neomycin. Nucleobase mutations in the apical loop, although distant from the binding pocke...

Adipose tissue macrophages (ATMs) display tremendous heterogeneity depending on signals in their local microenvironment and contribute to the pathogenesis of obesity. The phosphoinositide 3-kinase (PI3K) signalling pathway, antagonized by the phosphatase and tensin homologue (PTEN), is important for metabolic responses to obesity. We hypothesized t...

Flexible fitting is a powerful technique to build the 3D structures of biomolecules from cryoelectron microscopy (cryo-EM) density maps. One popular method is a cross-correlation coefficient-based approach, where the molecular dynamics (MD) simulation is carried out with the biasing potential that includes the cross-correlation coefficient between...

A synthetic riboswitch N1, inserted into the 5'-untranslated mRNA region of yeast, regulates gene expression upon binding ribostamycin and neomycin. Interestingly, a similar aminoglycoside, paromomycin, differing from neomycin by only one substituent (amino versus hydroxyl), also binds to the N1 riboswitch, but without affecting gene expression, de...

Synthetic oligonucleotides targeting functional regions of the prokaryotic rRNA could be promising antimicrobial agents. Indeed, such oligonucleotides were proven to inhibit bacterial growth. 2’-O-methylated (2’-O-Me) oligoribonucleotides with a sequence complementary to the decoding site in 16S rRNA were reported as inhibitors of bacterial transla...

Histograms of average stacking interactions per nucleotide in the regions targeted by 2’-O-Me oligomers in prokaryotic and eukaryotic decoding A-site models. For average and standard deviation values see Table 6 in the main text. (TIFF)

Standard error estimate for the RMSD and sum of VdW and electrostatic interaction between stacked nucleobases obtained with the average block analysis method. a) RMSD of the prokaryotic model, b) RMSD of the eukaryotic model, c) stacking energy of the prokaryotic model, d) stacking energy of the eukaryotic model. For the time-series of these values...

PAGE studies of 2’-O-Me oligoribonucleotides targeting prokaryotic and eukaryotic rRNA A-site models. For the rRNA and 2’-O-Me RNA sequences see Fig 2 in the main text. (TIFF)

A fragment of 23S ribosomal RNA (nucleotides 1906–1924 in E. coli), termed Helix 69, forms a hairpin that is essential for ribosome function. Helix 69 forms a conformationally flexible inter-subunit connection with helix 44 of 16S ribosomal RNA, and the nucleotide A1913 of Helix 69 influences decoding accuracy. Nucleotides U1911 and U1917 are post-...

Aminoglycoside antibiotics are protein synthesis inhibitors applied to treat infections caused mainly by aerobic Gram-negative bacteria. Due to their adverse side effects they are last resort antibiotics typically used to combat pathogens resistant to other drugs. Aminoglycosides target ribosomes. We describe the interactions of aminoglycoside anti...

Understanding the interactions which govern aminoglycoside antibiotic binding to ribosomal RNA is essential to propose modifications of these antibiotics. We have investigated the hydrogen bond patterns, solvent accessibility, and stacking energies of the nucleobases in twelve different aminoglycoside-RNA crystal complexes. These analyses pointed t...