MOLECULAR-DYNAMICS SIMULATIONS OF SIGNAL SEQUENCES AT A MEMBRANE WATER INTERFACE/

A recently developed software has been used to model peptides at a cyt oplasm/membrane mimetic environment where the interface is represented by a discontinuity in the dielectric constant. Molecular dynamics and energy minimization procedures available in the program were applied to a wild type and to a 50% active mutant (Delta 78r(1)) peptide signa l sequence of a lambda E. coli receptor (maltoporin). Modeling has bee n performed for both random coiled and constrained helical structures. As a general feature, the presence of the dielectric discontinuity in duced the movement of the molecules' center of mass toward the interfa ce. A decrease in the energy along interface crossing (from epsilon = 80 to epsilon = 2) was observed and interpreted as an indication of th eir affinity for the lipid-mimetic phase. Distinct patterns of migrati on were recognized for each sequence, as well as in different simulate d conditions for a same peptide. The random coiled peptides easily cro ss the interface, showing a tendency to go into the nonpolar phase, wh ereas constrained helical sequences tend to stay at the interface. Pot ential barriers and potential wells were identified in the modeling sp ace for constrained helical peptides, which have been shown to be depe ndent on the peptide primary sequence, on the conformational restricti ons imposed, and on the charge state of the peptide terminals.