Jan Walther Perthold

For many years, the calculation of free-energy differences involving a net-charge change from molecular simulations has been a challenge due to finite-size effect artifacts. Because of the nanoscopic scale of most simulation systems, long-range electrostatic interactions are either truncated at a given cutoff and subsequently approximated by a reaction field beyond the cutoff (1,2) or computed using lattice-sum methods.

We have designed a complete antibody-like construct where the C 1 and C domains are exchanged for a pair of the C 3 domains and efficient pairing of the heavy and light variable domain is achieved using “Knobs-into-Holes” strategy. This construct, composed of only naturally occurring immunoglobulin sequences without artificial linkers, expressed at a high level in mammalian cells, however exhibited low solubility.