An interval-based algorithm to represent conformational states of experimentally determined polypeptide templates and fast prediction of approximated 3D protein structures.

Predicting the three-dimensional (3-D) structure of a protein that has no templates in the Protein Data Bank (PDB) is a very hard, still an impossible task. Computational prediction methods have been developed during the last years, but the problem still remains challenging. In this paper we present a new strategy based on Interval Arithmetic to store structural information obtained from experimental protein templates and predict native-like approximate three-dimensional structures of proteins. Our objective is to perform the prediction in a very fast manner and predict native-like structures that can be used as starting point structures to ab initio methods. We illustrate the efficacy of our method in five case studies of polypeptides.

A structural model for chorismate synthase from Mycobacterium tuberculosis in complex with coenzyme and substrate.

The enzymes of the shikimate pathway constitute an excellent target for the design of new antibacterial agents; chorismate synthase (CS) catalyzes the last step of this pathway. The prediction of Mycobacterium tuberculosis (MTB) CS three-dimensional structure and the geometric docking of the coenzyme FMN and the substrate EPSP were performed using the crystal structure of CS from Streptococcus pneumoniae as template. Energy minimization of the whole complex showed, as expected, that most of the template interactions are preserved in the MTB structure, except for HIS11, ARG139 and GLN255. However, novel interactions involving ARG111, GLY113 and SER317 were also observed.