DFT and docking studies of rhodostreptomycins A and B and their interactions with solvated/nonsolvated Mg2+ and Ca2+ ions

• Published in: Journal of molecular modeling Vol. 19; no. 11; pp. 4823 - 4836
• Main Authors: Jardínez, Christiaan, Nicolás-Vázquez, Ines, Cruz-Borbolla, Julian, González-Ramírez, Cesar A., Cepeda, Miguel, Correa-Basurto, Jose, Pandiyan, Thangarasu, Miranda, Rene
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2013
• Subjects: Calcium - chemistry; Cations, Divalent - chemistry; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Hydrogen Bonding; Magnesium - chemistry; Models, Molecular; Molecular Docking Simulation; Molecular Medicine; Original Paper; Quantum Theory; Stereoisomerism; Streptomycin - analogs & derivatives; Streptomycin - chemistry; Theoretical and Computational Chemistry; Thermodynamics; Rhodostreptomycins A and B; DFT study; Mg; ions; and H; Ca
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-013-1952-3

The interactions of L -aminoglucosidic stereoisomers such as rhodostreptomycins A (Rho A) and B (Rho B) with cations (Mg 2+ , Ca 2+ , and H + ) were studied by a quantum mechanical method that utilized DFT with B3LYP/6-311G**. Docking studies were also carried out in order to explore the surface recognition properties of L -aminoglucoside with respect to Mg 2+ and Ca 2+ ions under solvated and nonsolvated conditions. Although both of the stereoisomers possess similar physicochemical/antibiotic properties against Helicobacter pylori , the thermochemical values for these complexes showed that its high affinity for Mg 2+ cations caused the hydration of Rho B. According to the results of the calculations, for Rho A–Ca 2+ (H 2 O) 6 , Δ H = −72.21 kcal mol −1 ; for Rho B–Ca 2+ (H 2 O) 6 , Δ H = −72.53 kcal mol −1 ; for Rho A–Mg 2+ (H 2 O) 6 , Δ H = −72.99  kcal mol −1 and for Rho B–Mg 2+ (H 2 O) 6 , Δ H  = −95.00  kcal mol −1 , confirming that Rho B binds most strongly with hydrated Mg 2+ , considering the energy associated with this binding process. This result suggests that Rho B forms a more stable complex than its isomer does with magnesium ion. Docking results show that both of these rhodostreptomycin molecules bind to solvated Ca 2+ or Mg 2+ through hydrogen bonding. Finally, Rho B is more stable than Rho A when protonation occurs. Figure Rho B–H showed higher stability since it is considered a proton pump inhibitor, and is therefore a stronger inhibitor of Helicobacter pylori