Balancing selectivity vs stability using molecular dynamics and umbrella sampling
- Jeremie Mortier†1Email author,
- Elisabeth K Nyakatura†1,
- Markus Miettinen2,
- Carsten Baldauf3,
- Gerhard Wolber1 and
- Beate Koksch1
© Mortier et al; licensee Chemistry Central Ltd. 2014
Published: 11 March 2014
This screen led to the identification of a novel core packing between VPE and VPK. One single consensus sequence was selected by the system, bearing a tyrosine in the hydrophobic core. Surprisingly, the dimer selected by phage display has a lower stability compared to the mother system. This important result raises the central question of selectivity vs stability. In order to address both aspects, theoretical investigations were conducted using molecular dynamics within the Gomacs suite. Pulling apart the two helices up to 3.00 nm from each other, potentials of mean force were calculated by umbrella sampling with a view to compare the energy barriers of the mother dimer to the phage display variant.
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