Direct use of 15N relaxation rates as experimental restraints on molecular shape and orientation for docking of...

(15)N relaxation rates contain information on overall molecular shape and size, as well as residue specific orientations of N-H bond vectors relative to the axes of the diffusion tensor. Here we describe a pseudopotential E(relax) that permits direct use of (15)N relaxation rates, in the form of R(2)/R(1) ratios, as experimental restraints in structure calculations without requiring prior information to be extracted from a known molecular structure. The elements of the rotational diffusion tensor are calculated from the atomic coordinates at each step of the structure calculation and then used together with the N-H bond vector orientations to compute the (15)N R(2)/R(1) ratios. We show that the E(relax) term can be reliably used for protein-protein docking of complexes and illustrate its applicability to the 40 kDa complex of the N-terminal domain of enzyme I and the histidine phosphocarrier protein HPr and to the symmetric HIV-1 protease dimer.