Molecular dynamics study on the influence of C-terminal sugar substitution on dynamics and conformation of vancomycin derivatives

ABSTRACT

Computational investigations were performed to examine the effects of the addition of 2-acetamido-2-deoxy-β-D-galactopyranosylamine or 1-amino-1-deoxy-D-glucitol connected to the C-terminus of vancomycin with different linkers. The purpose of this modification was to find more effective vancomycin derivatives by providing alternative interactions between vancomycin moiety and the peptidoglycan precursor. Each prepared vancomycin–peptidoglycan complex was optimized and submitted to the molecular dynamics study and analysis. The analysis of overall root mean square deviation, changes in position and interactions involving modified part of vancomycin as well as cluster analysis were carried out. One of the proposed vancomycin analogues seems to be efficient vancomycin substitute.

GRAPHICAL ABSTRACT

KEYWORDS:

• Vancomycin
• vancomycin derivatives
• molecular dynamics
• root mean square deviation
• conformational analysis

Acknowledgments

The computational time in the Academic Computer Center in Gdansk CI TASK, Poland is acknowledged. The authors would like to thank Klaudia Korzeniecka for her contribution to this work.

Funding

This work was supported by the European Union within the European Regional Development Fund under Grant UDA-POIG.01.01.02-14-102/09/05; University of Gdansk under Grant DS/530-8455-D-501-16.