The neuronal chemical synapse is an structurally and functionally highly complex interface of nerve cells. The molecular constitution and the manifold interactions of synaptic proteins is to great extent still unknown. Several functionally important synaptic processes do require calcium. The first part of this work characterizes the largest family of calcium-binding proteins, the EF Hand proteins. This family has been found to express a wide spectrum of conformations which make it difficult to functionally classify new proteins. To address this challenge a method has been developed to model new protein sequences into all possible conformers. That method of building conformational space models allowed the correct prediction of the myristoyl switch of the neuronal calcium sensor (NCS) protein VILIP and a new conformational transition state of NCS proteins. Additionally, the binding sites of EF Hand proteins of new interaction partners was found as e.g. the binding site of caldendrin on jacob. In the second part that method is used to efficiently design site directed mutations and subsequently analyze the transsynaptic neurexin/neuroligin complex. This complex seemed to play a unique role in synaptogenesis and maturation of the synaptic contact. Neurexins are cell surface proteins which bind to neuroligins forming a calcium dependent complex. This heterophilic complex is required for synaptic function and defects in genes of both proteins correlate with autism. The aim of this work was to use site directed mutagenesis to identify essential residues at the binding interface. Several model complex structures have been generated to facilitate the design mutations that completely block complex formation. It was found that EF hand motifs in neuroligin are degenerated and not required to bind to neurexin as suggested elsewhere. For the first time, calcium-45 binding to neurexin was detected. Performing multiple steps of modeling, mutagenesis and binding studies the binding site for neuroligin could be sharply delineated. Neuroligin binds to hydrophobic residues which surround the calcium-binding pocket and give the sixth LNS domain from alpha-neurexin and the LNS from beta-neurexin a unique property. Point mutations that changed electrostatic and shape properties leave calcium-coordination intact but completely inhibited neuroligin binding, whereas alternative splicing in alpha- and beta-neurexins and in neuroligins had a weaker effect on complex formation. In neuroligins, the contact area appears less distinct because exchange of a more distant aspartate completely abolished binding to neurexin but many mutations of predicted interface residues had no effect on binding. Calculating binding energies of wild-type and mutated complexes using the coordinates from recently determined beta-neurexin/neuroligin 1 crystal structures confirmed that the contact area in neurexin is rigid and invariable. Additional binding and comparative structural studies revealed that neurexin binds to all neuroligin isoforms using the same hydrophobic contact area. In contrast, neuroligin 2 does not fit into the complex structures of the other isoforms and may have an alternate binding area for neurexins.