Dresden 2017 – wissenschaftliches Programm
BP 56.7: Vortrag
Donnerstag, 23. März 2017, 16:45–17:00, SCH A251
The dynamics and flexibility of penicillin binding proteins: a combined computational/experimental approach to tackle antimicrobial resistance (AMR) — •Jasmine L. Desmond1, Pierdomenico Bellini2, Christopher Dowson2, P. Mark Rodger3, and Rudo A. Roemer1 — 1Department of Physics, University of Warwick, UK. — 2School of Life Sciences, University of Warwick, UK. — 3Department of Chemistry, University of Warwick, UK.
700,000 people die each year from drug-resistant infections, a figure that --- if action is not taken --- is estimated to increase to 10 million by 2050. The drug penicillin targets essential cell wall biosynthetic enzymes that still remain attractive targets for new efforts in drug discovery. Elucidating protein dynamics and flexibility is key to understanding the selective interactions of proteins with a drug as it docks. In spite of the success of x-ray crystallography in the determination of rigid protein structures, the experimental technique is unable to provide insight into the dynamics of proteins. Such information can, however, be elucidated using molecular modelling. Important protein conformational changes often occur on microsecond-millisecond timescales and are difficult to access using traditional modelling techniques, such as molecular dynamics (MD). Here, we present the results of computationally inexpensive, geometric simulations of protein motion for a range of penicillin binding proteins. There is a focus on differences in motion between: (1) inactive and active proteins and (2) proteins with and without bound drug molecules.