The modeling of biological molecules has led to great progress in the design of molecular structures with desired specific properties. Such products could be obtained synthetically or by genetic engineering procedures. Molecular modeling can lead to understanding of the dynamic situations compatible with experimental observations, permitting a formal definition of the conditions that would be theoretically expected to produce the observed behavior and therefore to infer patterns of behavior for situations of interest.
In this subject, THOR has been used to mimics a cytoplasm/membrane environment, with an interface separating two continuous media of different dielectric constants [1]. The computational code has been developed for the modelling of molecules of biological interest in aqueous and apolar media, as well as at the interface between them. The software establishes two media with different continuous dielectric constants, separated by an interface. The dielectric discontinuity is taken as an approximation of a cytoplasm/membrane environment.
The membrane/water interface is expressed by a discontinuity in the dielectric constant, taking into account the different electrical polarizability of the aqueous and the hydrocarbon phases. Then, the electrostatic interaction between nonbounded atoms at this interface will be renormalized by the influence of the dielectric discontinuity. The polarization field produced at the surface of discontinuity by a point charge can be calculated by the method of images. A fictitious charge is placed in the oppositive phase; the distance and the value of the image charge are fixed by taking the appropriate electrical boundary conditions at the surface.
When two charges i and j are on the same side of the interface,
the potential on i due to j will have a contribution due
to the image of j (i.e. j 
') , so that the Coulomb potential on i will be expressed by
where
is the distance between i and j atoms and
is the distance between i and 
, and x is the Cartesian coordinate of the surface between the two media.
when two charges are at different sides of the interface, the methods of
images gives the following results:
We note that the above terms account for the effect of the interface on the pair interaction terms only, the self-induced field created by a single charge being ignored here. The later will be a pure solvent effect which should be corrected by other solvent effects not treated here. Since we are most interested in the molecular conformational changes at the interface, we prefer only to consider the renormalization of the pair interactions, leading solvent effects for further investigations.
This approach were applied recently [1],[2]
to wild type and to a 50% active mutant ( 
78 r 
) peptide signal sequence of a 
E. coli receptor (moltoporin). Modeling has been performed for both random
coiled and constrained helical structures. As a general feature, the presence
of the dielectric discontinuity induced the movement of the molecules center
of mass toward the interface. A decrease in the energy along interface
crossing (from 
to 
) was observed and interpreted as an indication of their affinity for the
lipid-mimetic phase. Distinct patterns of migration were recognized for
each sequence, as well as in different simulated conditions for a same
peptide.
