StructureDistiller: Structural relevance scoring increases resilience of contact maps to false positive predictions

Abstract

AbstractProtein folding and structure prediction are two sides of the same coin. We propose contact maps and the related techniques of constraint-based structure reconstruction as unifying aspect of both processes. The presented Structural Relevance (SR) score quantifies the contribution of individual contacts and residues to structural integrity.It is demonstrated that entries of a contact map are not equally relevant for structural integrity. Structure prediction methods should explicitly consider the most relevant contacts for optimal performance because they effectively double resilience toward false positively predicted contacts. Furthermore, knowledge of the most relevant contacts significantly increases reconstruction fidelity on sparse contact maps by 0.4 Å.Protein folding is commonly characterized with spatial and temporal resolution: some residues are Early Folding while others are Highly Stable with respect to unfolding events. Using the proposed SR score, we demonstrate that folding initiation and structure stabilization are distinct processes.