Determination of contact maps in proteins: A combination of structural and chemical approaches

Contact map selection is a crucial step in structure-based molecular dynamics modelling of proteins. The map can be determined in many different ways. We focus on the methods in which residues are represented as clusters of effective spheres. One contact map, denoted as overlap (OV), is based on the overlap of such spheres. Another contact map, named Contacts of Structural Units (CSU), involves the geometry in a different way and, in addition, brings chemical considerations into account. We develop a variant of the CSU approach in which we also incorporate Coulombic effects such as formation of the ionic bridges and destabilization of possible links through repulsion. In this way, the most essential and well defined contacts are identified. The resulting residue-residue contact map, dubbed repulsive CSU (rCSU), is more sound in its physico-chemical justification than CSU. It also provides a clear prescription for validity of an inter-residual contact: the number of attractive atomic contacts should be larger than the number of repulsive ones - a feature that is not present in CSU. However, both of these maps do not correlate well with the experimental data on protein stretching. Thus, we propose to use rCSU together with the OV map. We find that the combined map, denoted as OV+rCSU, performs better than OV. In most situations, OV and OV+rCSU yield comparable folding properties but for some proteins rCSU provides contacts which improve folding in a substantial way. We discuss the likely residue-specificity of the rCSU contacts. Finally, we make comparisons to the recently proposed shadow contact map, which is derived from different principles.