Chapter 1: Introduction

The main purpose of the program FANTOM (Fast Newton - Raphson Torsion Angle Minimizer) is to efficiently calculate conformations of linear and cyclic polypeptides and proteins which have low conformational energies and are compatible with distance and dihedral angle constraints. These constraints, typically, are obtained from NMR experiments. The user can perform energy minimizations and Monte Carlo simulations of the ECEPP/2 empirical energy function. Protein-solvent interaction is included with a fast routine for the calculation of accessible surface areas of individual atoms and their gradients. In addition, FANTOM is suited for the exploration of low energy conformations of cyclic peptides or flexible loops in proteins. With the recently added program EXDIS (distributed with the present version), FANTOM can also generate "homology models" for a protein using a related protein structure as template.

FANTOM version 1.0 was based on the Newton-Raphson minimizer in torsion angle space, as described by Abe et al.. In version 2.0, several Monte Carlo algorithms (Metropolis algorithm with constant temperature, simulated annealing and adaptive temperature schedules) were added. Version 3.1 incorporated protein-solvent interaction energies calculated by a continuum approach where the atomic accessible surface areas and their gradients were calculated analytically according to Freyberg. Version 3.5 contained a Cartesian vector parametrization (PARAREA) of the accessible arcs. A built-in conjugate gradient minimizer made FANTOM independent of the corresponding routines of the NAG library (see the command switch). Version 4.0 contained several changes and improvements. The completely new surface & gradient routine GETAREA was based on a novel vector parametrization and a novel method of searching for the relevant vertices of accessible arcs. Another new feature of FANTOM 4.0 was the set of new commands for regularization of structures from the Brookhaven Protein Data Bank (PDB). The main change in the last version (4.1) was the introduction of a quasi-Newton minimizer based on the update formula of Broyden, Fletcher, Goldfarb and Shanno. Summaries are written out into separate files during calculations, to preserve partial results in case of a system crash. Provision was also made in version 4.1 to automatically recognize disulfide bridges in the input PDB files and to ignore hydrogen atoms at the user’s discretion.

The most important changes in the present version (4.2) are the incorporation of the new routine PATHWAY and the program EXDIS. Given two conformations A and B for a peptide/protein, the command pathway locates a low-energy path A ® B, by a series of energy minimizations in torsion angle space. This will find applications in the study of conformational transitions involving many dihedral angles. EXDIS accepts as input (1) an optimal amino acid alignment of the protein seqeunce to be modeled and that of a suitable template protein, and (2) the atomic coordinates for the template protein in PDB format. The files output by EXDIS are used as input by FANTOM to regularize and energy-minimize the model. We expect EXDIS/FANTOM to be very useful in homology modeling. The other new commands and options available in the present version have been introduced to enhance the analysis of models; e.g., the calculation of RMS deviations using different atom sets, calculation of the radii of gyration, and the analysis of side chain contacts.

This manual describes the installation (Chapter 2), the formats of input files (Chapter 3), the commands (Chapter 4), and output files (Chapter 5). Examples of the use of FANTOM are illustrated in Chapter 6. Error messages are generally explained in Chapter 7. Two new sections 4.6 and 4.7 describe homology modeling by EXDIS/FANTOM and the use of the new functionalty PATHWAY, respectively. Examples for these are given in Sections 6.6 and 6.7. Input files for all examples are included in the directories ex*. These files should be used to check FANTOM/EXDIS after a new installation. Please note that the output files for examples 6.1-6.5 correspond to the earlier version of FANTOM, and that the exact results obtained by running the current version 4.2 may differ slightly from those. Examples 6.6 and 6.7 are new and the results given correspond to the present version.

Descriptions of the algorithms used by the program can be found in references 1-4 and 6-15.

Comments, suggestions and bug reports are welcome. Please send them to:

Werner Braun
Sealy Center for Structural Biology
Department of Human Biological Chemistry & Genetics
University of Texas Medical Branch
Galveston, TX 77555-1157, U.S.A.
Fax: (409) 747-6850
Tel.: (409) 747-6810

The program can also be obtained via FTP. Please contact Prof. Braun for details.


This manual and the source code of the program FANTOM are copyrighted: (© 1995) by Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, CH - 8093 Zürich, Switzerland and (© 1997) University of Texas Medical Branch, Galveston, TX 77555, U.S.A