Protein Structure Determination via Distance GeometryStructural Similarity based Initialization

Abstract

The problem of finding the configuration of points given partial information on pairwise inter-point distances, the Euclidean distance geometry problem, appears in multiple applications. In this paper, we propose an approach that integrates structural similarity and a nonconvex distance geometry algorithm for the protein structure determination problem. When initialized with a homologous structure, reconstruction of ubiquitin structure with our non convex algorithm resulted in an RMSE of less than 2 [A] with 1.5% available inter proton distance and up to 20% relative error in the input distances. To test the robustness of this algorithm with regard to initialization, we also initialized with a nonhomologous structure on a larger protein with pdb coordinate 1W2E. Even though the initialization structure 1JYB is far different from 1W2E with an RMSE of 25 [A], reconstruction generated structures with RMSE of close to 2 [A], using 1.7% available proton distances and up to 10% relative error in input distances. These results suggest EDG-based approach may be applied to fast NMR structure determination in the future.