A series of macrocycles consisting of 9,10-substituted phenanthrenes connected by butadiynylene linkers in positions 3 and 6 has been described as well as their transformation into the corresponding phenanthrylene-thienylene macrocycles. Structure and properties of the macrocycles, such as self-association in solution and optical and electrochemical properties, were studied and reported in a comparative manner with respect to the effects of the different sizes and shapes of the macrocycles and the character and length of their side chains.

• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Knowledge of the structure and conformational flexibility of carbohydrates in an aqueous solvent is important to improving our understanding of how carbohydrates function in biological systems. In this study, we extend a variant of the Hamiltonian replica-exchange molecular dynamics (MD) simulation to improve the conformational sampling of saccharides in an explicit solvent. During the simulations, a biasing potential along the glycosidic-dihedral linkage between the saccharide monomer units in an oligomer is applied at various levels along the replica runs to enable effective transitions between various conformations. One reference replica runs under the control of the original force field. The method was tested on disaccharide structures and further validated on biologically relevant blood group B, Lewis X and Lewis A trisaccharides. The biasing potential-based replica-exchange molecular dynamics (BP-REMD) method provided a significantly improved sampling of relevant conformational states compared with standard continuous MD simulations, with modest computational costs. Thus, the proposed BP-REMD approach adds a new dimension to existing carbohydrate conformational sampling approaches by enhancing conformational sampling in the presence of solvent molecules explicitly at relatively low computational cost.

• Klíčová slova
• adaptive biasing force simulations, biasing potential replica-exchange simulation, conformational sampling, molecular dynamics simulation, saccharides,
• MeSH
• antigeny krevních skupin chemie   genetika   MeSH
• disacharidy chemie   genetika   MeSH
• konformace sacharidů MeSH
• lidé MeSH
• sekvenční analýza * MeSH
• simulace molekulární dynamiky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny krevních skupin MeSH
• disacharidy MeSH

The linear interaction energy (LIE) method to compute binding free energies is applied to lectin-monosaccharide complexes. Here, we calculate the binding free energies of monosaccharides to the Ralstonia solanacearum lectin (RSL) and the Pseudomonas aeruginosa lectin-II (PA-IIL). The standard LIE model performs very well for RSL, whereas the PA-IIL system, where ligand binding involves two calcium ions, presents a major challenge. To overcome this, we explore a new variant of the LIE model, where ligand-metal ion interactions are scaled separately. This model also predicts the saccharide binding preference of PA-IIL on mutation of the receptor, which may be useful for protein engineering of lectins.

• MeSH
• lektiny chemie   MeSH
• ligandy MeSH
• molekulární modely MeSH
• monosacharidy chemie   MeSH
• Pseudomonas aeruginosa chemie   MeSH
• Ralstonia solanacearum chemie   MeSH
• simulace molekulární dynamiky * MeSH
• termodynamika * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lektiny MeSH
• ligandy MeSH
• monosacharidy MeSH

Carbohydrate-receptor interactions are an integral part of biological events. They play an important role in many cellular processes, such as cell-cell adhesion, cell differentiation and in-cell signaling. Carbohydrates can interact with a receptor by using several types of intermolecular interactions. One of the most important is the interaction of a carbohydrate's apolar part with aromatic amino acid residues, known as dispersion interaction or CH/π interaction. In the study presented here, we attempted for the first time to quantify how the CH/π interaction contributes to a more general carbohydrate-protein interaction. We used a combined experimental approach, creating single and double point mutants with high level computational methods, and applied both to Ralstonia solanacearum (RSL) lectin complexes with α-L-Me-fucoside. Experimentally measured binding affinities were compared with computed carbohydrate-aromatic amino acid residue interaction energies. Experimental binding affinities for the RSL wild type, phenylalanine and alanine mutants were -8.5, -7.1 and -4.1 kcal x mol(-1), respectively. These affinities agree with the computed dispersion interaction energy between carbohydrate and aromatic amino acid residues for RSL wild type and phenylalanine, with values -8.8, -7.9 kcal x mol(-1), excluding the alanine mutant where the interaction energy was -0.9 kcal x mol(-1). Molecular dynamics simulations show that discrepancy can be caused by creation of a new hydrogen bond between the α-L-Me-fucoside and RSL. Observed results suggest that in this and similar cases the carbohydrate-receptor interaction can be driven mainly by a dispersion interaction.

• MeSH
• aminokyseliny aromatické chemie   genetika   metabolismus   MeSH
• bakteriální proteiny chemie   genetika   metabolismus   MeSH
• fukosa chemie   metabolismus   MeSH
• konformace proteinů MeSH
• konformace sacharidů MeSH
• krystalografie rentgenová MeSH
• lektiny chemie   genetika   metabolismus   MeSH
• molekulární modely * MeSH
• mutace MeSH
• proteiny chemie   genetika   metabolismus   MeSH
• Ralstonia solanacearum genetika   metabolismus   MeSH
• sacharidy chemie   MeSH
• sekundární struktura proteinů MeSH
• terciární struktura proteinů MeSH
• termodynamika MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny aromatické MeSH
• bakteriální proteiny MeSH
• fukosa MeSH
• lektiny MeSH
• proteiny MeSH
• sacharidy MeSH

In this study, in silico mutagenesis and docking in Ralstonia solanacearum lectin (RSL) were carried out, and the ability of several docking software programs to calculate binding affinity was evaluated. In silico mutation of six amino acid residues (Agr17, Glu28, Gly39, Ala40, Trp76, and Trp81) was done, and a total of 114 in silico mutants of RSL were docked with Me-α-L-fucoside. Our results show that polar residues Arg17 and Glu28, as well as nonpolar amino acids Trp76 and Trp81, are crucial for binding. Gly39 may also influence ligand binding because any mutations at this position lead to a change in the binding pocket shape. The Ala40 residue was found to be the most interesting residue for mutagenesis and can affect the selectivity and/or affinity. In general, the docking software used performs better for high affinity binders and fails to place the binding affinities in the correct order.

• MeSH
• krystalografie rentgenová MeSH
• lektiny chemie   genetika   metabolismus   MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• mutageneze MeSH
• počítačová simulace * MeSH
• Ralstonia solanacearum chemie   genetika   metabolismus   MeSH
• receptory buněčného povrchu chemie   MeSH
• sacharidové sekvence MeSH
• software * MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lektiny MeSH
• receptory buněčného povrchu MeSH
• saccharide-binding proteins MeSH Prohlížeč