'Hybrid protein model' for optimally defining 3D protein structure fragments

Abstract

Motivation: Our aim is to develop a process that automatically defines a repertory of contiguous 3D protein structure fragments and can be used in homology modeling. We present here improvements to the method we introduced previously: the 'hybrid protein model' (de Brevern and Hazout, Theor. Chem. Acc., 106, 36-47, 2001) The hybrid protein learns a non-redundant databank encoded in a structural alphabet composed of 16 Protein Blocks (PBs; de Brevern et al., Proteins, 41, 271-287, 2000). Every local fold is learned by looking for the most similar pattern present in the hybrid protein and modifying it slightly. Finally each position corresponds to a cluster of similar 3D local folds. Results: In this paper, we describe improvements to our method for building an optimal hybrid protein: (i) 'baby training,' which is defined as the introduction of large structure fragments and the progressive reduction in the size of training fragments; and (ii) the deletion of the redundant parts of the hybrid protein. This repertory of contiguous 3D protein structure fragments should be a useful tool for molecular modeling.