New Error Measures and Methods for Realizing Protein Graphs from Distance Data

• Published in: Discrete & computational geometry Vol. 57; no. 2; pp. 371 - 418
• Main Authors: D’Ambrosio, Claudia, Vu, Ky, Lavor, Carlile, Liberti, Leo, Maculan, Nelson
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-03-2017; Springer Nature B.V; Springer Verlag
• Subjects: Backbone; Combinatorics; Computational mathematics; Computational Mathematics and Numerical Analysis; Computer Science; Error analysis; Errors; Euclidean space; Geometry; Graph theory; Graphs; Intervals; Mathematical analysis; Mathematical models; Mathematics; Mathematics and Statistics; Operations Research; Proteins; Protein conformation; Distance geometry; Mathematical programming; protein conformation; mathematical programming; distance geometry
• ISSN: 0179-5376; 1432-0444
• DOI: 10.1007/s00454-016-9846-7

The interval distance geometry problem consists in finding a realization in
R
K
of a simple undirected graph
G
=
(
V
,
E
)
with non-negative intervals assigned to the edges in such a way that, for each edge, the Euclidean distance between the realization of the adjacent vertices is within the edge interval bounds. In this paper, we focus on the application to the conformation of proteins in space, which is a basic step in determining protein function: given interval estimations of some of the inter-atomic distances, find their shape. Among different families of methods for accomplishing this task, we look at mathematical programming based methods, which are well suited for dealing with intervals. The basic question we want to answer is: what is the
best
such method for the problem? The most meaningful error measure for evaluating solution quality is the coordinate root mean square deviation. We first introduce a new error measure which addresses a particular feature of protein backbones, i.e. many partial reflections also yield acceptable backbones. We then present a set of new and existing quadratic and semidefinite programming formulations of this problem, and a set of new and existing methods for solving these formulations. Finally, we perform a computational evaluation of all the feasible solver 
+
 formulation combinations according to new and existing error measures, finding that the best methodology is a new heuristic method based on multiplicative weights updates.