A space-time structure determination of human CD2 reveals the CD58-bindingmode

We describe a procedure for a space-time description of protein structures. The method is capable of determining populations of conformational substat es, and amplitudes and directions of internal protein motions, This is achi eved by fitting static and dynamic NMR data, The approach is based on the j umping-among-minima concept, First, a wide conformational space compatible with structural NMR data is sampled to find a large set of substates, Subse quently, intrasubstate motions are sampled by using molecular dynamics calc ulations with force field energy terms, Next, the populations of substates are fitted to NMR relaxation data. By diagonalizing a second moment matrix, directions and amplitudes of motions are identified, The method was applie d to the adhesion domain of human CD2. We found that very few substates can account for most of the experimental data. Furthermore, only two types of collective motions have high amplitudes. They represent transitions between a concave (closed) and flat (open) binding face and resemble the change up on counter-receptor (CD58) binding.