A Crystallographic and Molecular Dynamics Simulation Study of Protein Crystallization

(M.Sc. Johannes Hermann)

Crystallization of alcohol dehydrogenase from Lactobacillus brevis and mutants was modeled in silico. Neutron and X-ray crystallography allowed the generation of valid crystal structure models as input for subsequent molecular dynamics free energy simulations. Protein nucleation and crystal growth is guided by thermodynamically stabilizing interactions at crystal contacts. Free energy guided design of protein variants was found to be a powerful new tool to control protein crystallization.

Publications

• Hermann J, Bischoff D, Grob P, Janowski R, Hekmat D, Niessing D, Zacharias M, Weuster-Botz D (2021): Controlling protein crystallization by free energy guided design of interactions at crystal contacts. Crystals 11: 588.
• Grob P, Huber M, Walla B, Hermann J, Janowski R, Niessing D, Hekmat D, Weuster-Botz D (2020): Crystal contact engineering enables efficient capture and purification of an oxidoreductase by technical crystallization. Biotechnol J 15: 2000010.
• Nowotny P, Hermann J, Li J, Krautenbacher AE, Klöpfer K, Hekmat D, Weuster-Botz D (2019): Rational crystal contact engineering of Lactobacillus brevis alcohol dehydrogenase to promote technical protein crystallization. Crystal Growth and Design 19: 2380–2387.
• Hermann J, Nowotny P, Schrader TE, Biggel P, Hekmat D, Weuster-Botz D (2018): Neutron and X-ray crystal structures of Lactobacillus brevis alcohol dehydrogenase reveal new insights on hydrogen bonding pathways. Acta Cryst F74: 754-764.