Crystallographic threading.

Abstract

Crystallographic studies play a major role in current efforts towards protein structure determination. Despite recent advances in computational tools for molecular modeling and graphics, the construction of a three-dimensional protein backbone model from crystallographic data remains complex and time-consuming. This paper describes a unique contribution to an automated approach to protein model construction and evaluation, where a model is represented as an annotated trace (or partial trace) of a structure. Candidate models are derived through a topological analysis of the electron density map of a protein. Using sequence alignment techniques, we determine an optimal threading of the known sequence onto the candidate protein structure models. In this threading, connected nodes on the model are associated with adjacent amino acids in the sequence and a fitness score is assigned based on features extracted from the electron density map for the protein. Experimental results demonstrate that crystallographic threading provides an effective means for evaluating the "goodness" of experimentally derived protein models.