Fidelity of the protein structure reconstruction from inter-residue proximity constraints

Inter-residue proximity constraints obtained in such experiments as cross-linking/mass spectrometry are important sources of information for protein structure determination. A central question in structure determination using these constraints is, What is the minimal number of inter-residue constraints needed to determine the fold of a protein? It is also unknown how the different structural aspects of constraints differentiate their ability in determining the native fold and whether there is a rational strategy for selecting constraints that feature higher fidelity in structure determination. To shed light on these questions, we study the fidelity of protein fold determination using theoretical inter-residue proximity constraints derived from protein native structures and the effect of various subsets of such constraints on fold determination. We show that approximately 70% randomly selected constraints are sufficient for determining the fold of a domain (with an average root-mean-square deviation of