Aggregation of Kanamycin A: dimer formation with physiological cations
Johannes M Dieterich1, Ulrich Gerstel, Jens-Michael Schröder
1Institut für Physikalische Chemie, Christian-Albrechts-Universität, Olshausenstraße 40, 24098 Kiel, Germany.
Journal of Molecular Modeling
|March 3, 2011
Summary
This study demonstrates global cluster geometry optimization for flexible molecules, supporting experimental findings on Kanamycin A (KA) clustering with sodium cations. Theoretical analysis reveals KA-sodium interactions are preferred over KA-potassium interactions.
Area of Science:
- Computational chemistry
- Molecular modeling
- Biophysical chemistry
Background:
- Global cluster geometry optimization traditionally focused on atoms or compact molecules.
- Experimental studies suggest Pseudomonas aeruginosa forms larger clusters of Kanamycin A (KA) with specific cations.
Purpose of the Study:
- To demonstrate the feasibility of global optimization for extended, flexible molecules.
- To provide theoretical support for observed Kanamycin A (KA) clustering.
- To investigate cation preference in KA clusters.
Main Methods:
- Global cluster structure optimization.
- Application of force fields, semiempirical, DFT, and ab-initio methods.
- Analysis of monomer, bare dimer, and cation-bound dimer structures.
Main Results:
- Theoretical support for Kanamycin A (KA) clustering.
- Demonstrated preference for sodium over potassium cations in KA clusters due to distinct embedding.
- Predicted NMR and IR spectra for experimental detection of aggregation state and cation binding.
Conclusions:
- Present-day computational techniques enable global optimization of extended, flexible molecular clusters.
- Theoretical findings align with experimental observations of cation preference in KA clusters.
- Predicted spectroscopic signatures offer avenues for experimental validation.
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