Understanding the energetics and architecture of protein binding interfaces is important for basic research and could potentially facilitate the design of novel binding domains for biotechnological applications. It is well accepted that a few key residues at binding interfaces termed hot-spots of binding are responsible for contributing most of the binding free energy. We introduced a new concept of binding cold-spots, or interface positions occupied by suboptimal amino acids. Such positions exhibit a potential for affinity enhancement through various mutations. We perform analysis of the whole PDB to study cold-spot frequency, their structural distribution and conservation pattern. Identification of cold-spot positions is crucial for studies of protein evolution and for design of new therapeutical molecules.