To be folded, to be unfolded or to be aggregated with important functions: application of the directed coaggregation mechanism to combat bacterial communities

One of the reasons for the mortal danger to humans is the ability of pathogenic bacteria to form biofilms. The formation of biofilms is an evolutionarily conservative defense mechanism against adverse conditions. The use of this protection by pathogenic bacteria reduces the effectiveness of the main means of combating them - antibiotics, which complicates the production of new types of drugs. There are two types of antimicrobial agents that are not known antibiotics: nanoparticles and antimicrobial peptides. We demonstrated that peptides synthesized based on the amino acid sequence of proteins and capable of amyloid formation and coaggregation with the whole protein exhibit antimicrobial activity. The ability of peptides to coaggregate with target proteins can help combat biofilm-forming bacterial communities. We evaluated the antimicrobial effects of ten synthesized hybrid peptides, which were obtained based on the sequences of the S1 ribosomal protein of P. aeruginosa and S. aureus. It is important that some peptides demonstrated high antimicrobial activity comparable to the antibiotic gentamicin sulfate against pathogenic strains of MRSA, S. aureus, and P. aeruginosa. These peptides showed no toxicity to eukaryotic cells. Our study demonstrates the promise of hybrid peptides based on the amyloidogenic regions of the S1 ribosomal protein for the development of new antimicrobials against Gram-positive and Gram-negative bacteria resistant to traditional antibiotic.Belgrade : Institute of molecular genetics and genetic engineerin

Inclusion of the Most Important Multi-Particle Interactions in the Amber Force Field and Application of the Revised Force Field To Molecular Dynamics Calculations

Выведены формулы для расчета потенциалов и сил в новом силовом поле невалентных взаимодействий, включающем, наряду с традиционными членами, наведенную парциальными зарядами поляризацию всех атомов и трехчастичные дисперсионные взаимодействия «атом – валентная связь». Соответствующие новые члены добавлены к стандартному силовому полю АМБЕР. Проведены молекулярно-динамические расчеты с использованием обновленного силового поля. Показано, что добавленные, физически разумные члены не сильно замедляют молекулярно-динамическое моделирование, несмотря на то, что они учитывают важнейшие трехчастичные взаимодействия. Formulas for calculation of energy and forces in the new force field of non bonded interactions including along with traditional members, the polarization, induced by partial atomic charges, and three-particle dispersive interactions of the atoms with covalent bonds are received. The corresponding new members are added to a standard AMBER force field. Molecular dynamics calculations with the use of the updated force field are carried out. It is shown that additional physically reasonable members, taking into account the major three-particle interactions, not strongly slow down molecular dynamics simulation