Abstract:

A well-known problem in protein modeling is the determination of the structure of a protein with a given set of inter-atomic or inter-residue distances obtained from either physical experiments or theoretical estimates. A general form of the problem is known as the distance geometry problem in mathematics, the graph embedding problem in computer science, and the multidimensional scaling problem in statistics. The problem has applications in many other scientific and engineering fields as well such as sensor network localization, image recognition, and protein classification. We describe the formulations and complexities of the problem in its various forms, and introduce a so-called geometric buildup approach to the problem. We present the general algorithm and discuss related computational issues including control of numerical errors, determination of rigid vs. unique structures, and tolerance of distance errors. The theoretical basis of the approach is established based on the theory of distance geometry. A group of necessary and sufficient conditions for the determination of a structure with a given set of distances using a geometric buildup algorithm are justified. The applications of the algorithm to model protein problems are demonstrated.