NORMA: a tool for flexible fitting of high-resolution protein structures into low-resolution electron-microscopy-derived density maps

Karsten Suhre,Jorge Navaza,Yves-Henri Sanejouand

doi:10.1107/s090744490602244x

Abstract

This paper describes a freely available software suite that allows the modelling of large conformational changes of high-resolution three-dimensional protein structures under the constraint of a low-resolution electron-density map. Typical applications are the interpretation of electron-microscopy data using atomic scale X-ray structural models. The software package provided should enable the interested user to perform flexible fitting on new cases without encountering major technical difficulties. The NORMA software suite including three fully executable reference cases and extensive user instructions are available at http://www.elnemo.org/NORMA/.

Highlights

High-quality three-dimensional reconstructions of large protein assemblies are increasingly becoming available owing to recent advances in cryo-electron microscopy (EM) and related technologies
A determination of the related conformational changes can help in the interpretation of the EM observations, but in addition yield valuable information about the functional movements of the proteins involved. It has been shown in the past that large conformational changes often correspond to highly collective movements that can be described well by a small number of low-frequency normal modes of that protein (Harrison, 1984; Krebs et al, 2002; Marques & Sanejouand, 1995; McCammon et al, 1976; Perahia & Mouawad, 1995; Tama & Sanejouand, 2001; Yang & Bahar, 2005)
The application of normal-mode flexible fitting into EM density maps has been formally introduced by Tama et al (2004a)

Summary

Biological Crystallography

Karsten Suhre,a* Jorge Navazab and Yves-Henri Sanejouandc aGenomics and Structural Information Laboratory, Institut de Biologie Structurale et Microbiologie, UPR 2589 CNRS, Marseille, France, bLMES, Institut de Biologie Structurale Jean-Pierre Ebel, UMR 5075 CEA–CNRS– Universite Joseph Fourier, Grenoble, France, and cLaboratoire de Physique, UMR 5672 of CNRS, Ecole Normale Superieure, Lyon, France. NORMA: a tool for flexible fitting of high-resolution protein structures into low-resolution electron-microscopy-derived density maps. This paper describes a freely available software suite that allows the modelling of large conformational changes of high-resolution three-dimensional protein structures under the constraint of a low-resolution electron-density map. Typical applications are the interpretation of electron-microscopy data using atomic scale X-ray structural models. The software package provided should enable the interested user to perform flexible fitting on new cases without encountering major technical difficulties. The NORMA software suite including three fully executable reference cases and extensive user instructions are available at http:// www.elnemo.org/NORMA/. # 2006 International Union of Crystallography Printed in Denmark – all rights reserved

Introduction

Findings

Concluding remarks