Tables for
Volume F
Crystallography of biological macromolecules
Edited by M. G. Rossmann and E. Arnold

International Tables for Crystallography (2006). Vol. F, ch. 25.1, p. 689

Section 25.1.5. Structure refinement

J. Dinga* and E. Arnoldb

aBiomolecular Crystallography Laboratory, CABM & Rutgers University, 679 Hoes Lane, Piscataway, NJ 08854-5638, USA, and Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Yue-Yang Road, Shanghai 200 031, People's Republic of China, and bBiomolecular Crystallography Laboratory, CABM & Rutgers University, 679 Hoes Lane, Piscataway, NJ 08854-5638, USA
Correspondence e-mail:

25.1.5. Structure refinement

| top | pdf |

Several program packages that are used for structure refinement are described in Section 25.1.2[link]. These include CNS, X-PLOR, BIOMOL, PHASES and PROTEIN. See Section 25.1.2[link] for further information. ARP/wARP

| top | pdf |

The Automated Refinement Procedure, ARP/wARP (Lamzin & Wilson, 1993[link], 1997[link]), is a program package for automated model building and refinement of protein structures. It combines, in an iterative manner, reciprocal-space structure-factor refinement with updating of the model in real space to construct and improve protein models. ARP/wARP can also be used for ab initio structure solution of metalloproteins at high resolution. ARP/wARP is distributed as part of the CCP4 suite (Section[link]. See Section 25.2.5[link] for a detailed description.

Location: . Operating systems: UNIX, HPUX, IRIX and LINUX. Type: source code and binary. Language: Fortran77. Distribution: free academic. MULTAN88

| top | pdf |

MULTAN88 (Main et al., 1980[link]) is a program that uses direct methods to determine crystal structures from single-crystal diffraction data. It can be used for very high resolution structure refinement and determination of heavy-atom positions.

Location: . Operating systems: UNIX and VAX/VMS. Type: binary. Distribution: commercial. PROLSQ

| top | pdf |

PROLSQ (Hendrickson & Konnert, 1979[link]) is used for the restrained least-squares refinement of a protein structure. Prior to running PROLSQ, the program PROTIN must be run to analyse the protein geometry and produce an output file containing restraints information. PROLSQ cannot calculate structure factors. Use SFALL to calculate X-ray contributions to the matrix. PROLSQ is distributed as a unsupported program of the CCP4 suite (Section[link].

Location: . Operating systems: UNIX, VAX/VMS and LINUX. Type: source code and binary. Distribution: free academic. REFMAC

| top | pdf |

REFMAC (Murshudov et al., 1997[link], 1999[link]) is a macromolecular refinement program which has been integrated into the CCP4 suite (Section[link]. REFMAC can carry out rigid-body, restrained or unrestrained refinement against X-ray data, or idealization of a macromolecular structure. It minimizes the coordinate parameters to satisfy either a maximum-likelihood or least-squares residual. There are options to use different minimization methods. If the user wishes to invoke geometric restraints, the program PROTIN, which analyses the protein geometry and produces an output file containing restraints information, must be run prior to running REFMAC. REFMAC also produces an MTZ output file containing weighted coefficients for SIGMAA-weighted mFo-DFcalc and 2mFo-DFcalc maps, where `missing data' have been restored.

Location: . Operating systems: UNIX, SGI, SUN, DEC and LINUX. Type: source code and binary. Distribution: free. RSRef

| top | pdf |

RSRef (Chapman, 1995[link]) is a package of programs that enables an atomic model to be optimized by fitting to an electron-density map. RSRef uses an electron-density function that is resolution dependent, so that it accurately models a medium-resolution map. When combined with TNT's (Section[link] Geometry, full stereochemical refinement is possible. RSRef can be used to quickly pre-refine a protein structure during or after model building, or to completely refine structures with high noncrystallographic symmetry that have good electron density.

Location:∼rsref/ . Operating systems: SGI and EVS. Type: source code and binary. Distribution: minor licence fee for academic users. SHELX97

| top | pdf |

SHELX (Sheldrick & Schneider, 1997[link]) is a set of programs for crystal structure determination from single-crystal diffraction data. Originally SHELX was intended only for small molecules. However, improvements in computing performance and data-collection methods have led to increased use of SHELX for macromolecules, especially the location of heavy atoms from isomorphous and anomalous-difference data, and the refinement of proteins against high-resolution data (2.5 Å or better). See Section 25.2.10[link] for a detailed description.

Location: . Operating systems: UNIX, VMS, DOS and Windows. Type: binary. Language: Fortran77. Distribution: free academic. SIR97

| top | pdf |

SIR97 (Altomare et al., 1999[link]) is an integrated program package for the determination and refinement of small-molecule structures from single-crystal diffraction data. It is also useful in solving the heavy-atom positions in protein structure determination.

Location: . Operating systems: UNIX, VMS, MacOS and Windows. Type: binary. Distribution: free academic. TNT

| top | pdf |

TNT (Tronrud et al., 1987[link]; Tronrud, 1997[link]) is a general-purpose program package for the structure refinement of macromolecules using single-crystal X-ray diffraction data. It is normally used to optimize a model to X-ray diffraction data while maintaining proper stereochemistry using least-squares function-minimization techniques. It can restrain a model to bond lengths, bond angles, dihedral angles, pseudo-rotation angles, planarity and non-bonded `close' contacts (including symmetry-related contacts). A principal advantage of the TNT package is its great flexibility, making it ideal for restraining structures that contain cofactors, inhibitors, or nucleic acids. The package is composed of separate programs, each performing clearly defined tasks. To use the package with other forms of data you simply write programs that produce the value and first derivative of the functional term you wish to minimize. See Section 25.2.4[link] for a detailed description.

Location: . Operating systems: UNIX, VAX/VMS, DEC Alpha, EVS, AIX, SUN and SGI. Type: source code and binary. Distribution: free academic.


Altomare, A., Burla, M. C., Camalli, M., Cascarano, G., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). SIR97: a new tool for crystal structure determination and refinement. J. Appl. Cryst. 32, 115–119.Google Scholar
Chapman, M. S. (1995). Restrained real-space macromolecular atomic refinement using a new resolution-dependent electron-density function. Acta Cryst. A51, 69–80.Google Scholar
Hendrickson, W. A. & Konnert, J. H. (1979). Stereochemically restrained crystallographic least-squares refinement of macromolecule structures. In Biomolecular structure, conformation, function and evolution, edited by R. Srinivasan, Vol. I, pp. 43–57. New York: Pergamon Press.Google Scholar
Lamzin, V. S. & Wilson, K. S. (1993). Automated refinement of protein models. Acta Cryst. D49, 129–147.Google Scholar
Lamzin, V. S. & Wilson, K. S. (1997). Automated refinement for protein crystallography. Methods Enzymol. 277, 269–305.Google Scholar
Main, P., Fiske, S. J., Hull, S. E., Lessinger, L., Germain, G., Declercq, J.-P. & Woolfson, M. M. (1980). MULTAN80. A system of computer programs for the automatic solution of crystal structures from X-ray diffraction data. Universities of York, England, and Louvain, Belgium.Google Scholar
Murshudov, G. N., Vagin, A. A. & Dodson, E. J. (1997). Refinement of macromolecular structures by the maximum-likelihood method. Acta Cryst. D53, 240–255.Google Scholar
Murshudov, G. N., Vagin, A. A., Lebedev, A., Wilson, K. S. & Dodson, E. J. (1999). Efficient anisotropic refinement of macromolecular structures using FFT. Acta Cryst. D55, 247–255.Google Scholar
Sheldrick, G. M. & Schneider, T. R. (1997). SHELXL: high-resolution refinement. Methods Enzymol. 277, 319–343.Google Scholar
Tronrud, D. E. (1997). The TNT refinement package. Methods Enzymol. 277, 306–319.Google Scholar
Tronrud, D. E., Ten Eyck, L. F. & Matthews, B. W. (1987). An efficient general-purpose least-squares refinement program for macromolecular structures. Acta Cryst. A43, 489–501.Google Scholar

to end of page
to top of page