ProFASi: The Protein Folding and Aggregation Simulator

Version 1.1

Introduction

PROFASI (PROtein Folding and Aggregation SImulator [I]) is a C++ program package for Monte Carlo simulations of protein folding and aggregation. It provides an implementation of an all-atom protein model with fixed bond lengths and bond angles, an implicit water simplified force field, and a set of tools to perform Monte Carlo simulations with the model.

Folding simulations of a protein with both helical and $\beta$ -sheet secondary structure and a non-trivial geometry. Click here to go to a gallery of folding and aggregation studies done with PROFASI.

A $\beta$ -barrel oligomer observed in 9-chain simulations of $A\beta_{16-22}$ peptides. Click here to go to a gallery of folding and aggregation studies done with PROFASI.

This documentation refers to PROFASI version 1.1, publicly available from 29 May 2008. The current version is version 1.1.6, which can be generated from the distributed version 1.1.2 by applying patches available in the PROFASI updates page. The documentation is automatically generated using the doxygen program. If doxygen is installed on your system, you can generate this documentation locally on your computer by running "doxygen Doxyfile" in the main PROFASI directory. An up-to-date version of every documentation page as well as other information about the package can be obtained from the PROFASI homepage.

The model implemented in PROFASI successfully describes the folding and thermodynamic behaviour of a number of peptides of both $\alpha$ -helical and $\beta$ -sheet secondary structure with about 20 residues [II, III]. At least on one instance, it also describes the folding of a 49-residue protein with both $\alpha$ -helical and $\beta$ -sheet secondary structure elements and a complex topology [IV], using unbiased replica exchange Monte Carlo simulations starting from random initial conformations.

PROFASI has been used in a number of studies of amyloid aggregation, with up to 30 peptide chains in full atomic detail [V, VI, VII]. Other interesting applications include studies of mechanical and thermal unfolding of globular proteins [VIII, IX, X] as well as studies of small semiconductor-binding peptides [XI].

For a detailed description of the model and the interaction potential, please refer to [II]. A gallery of some interesting simulations done with this program can be found here. If any publication should result using this program package, please cite it through [I] and the web address of the program: "http://cbbp.thep.lu.se/activities/profasi/".

PROFASI is freely available under a licence similar to the GNU General Public Licence, but is restricted to academic users.

If you have requested/received PROFASI in the past, you are in our user list. You do not need to send a new PROFASI request through the PROFASI webpage. In case there is a special reason that prevents you from using the patch files to update from PROFASI 1.1.2 to the current version, please send a mail to profasi at thep dot lu dot se, and we will forward the latest version of the package to you.

If you would like to get a copy of the PROFASI code, please go to the PROFASI request page. On that page you will be presented with a form to provide a little information about yourself, including your email address. We are unable to send the package to email addresses not belonging to academic and research institutions.
Please check the updates page from time to time and download patches fixing various problems or providing additional functionality.
We welcome your involvement in this project. If you use PROFASI and find errors in the code, causing it to crash where it should not, give wrong answers, hang etc., we would appreciate if you send a note to "profasi at thep.lu.se". Even better, if you fix the problem yourself, it would be a nice thing to do to share it with other people using PROFASI for their research. Please send a patch file containing your fix/enhancement to the same email address. We will review the patch and do the necessary corrections to ensure compatibility with other changes in the code, and then make the patch available in the PROFASI updates page, with due credit to you. A patch will be considered for inclusion if and only if it does not break the build.

For a quick introduction to get started with PROFASI take a look at Tutorial 1: A half an hour tour of PROFASI . Whether or not you have any experience with the program, this tutorial should give you a feel for it quickly.
If you have used PROFASI v 1.0 for some time, you can get an idea of the main changes in this version by reading New in PROFASI version 1.1
For a structured view of the design of PROFASI, you should look at the Modules pages of this documentation.
For a list of ready-made application programs you can use directly to do simulations and analyze data, and other related information, please take a look at PROFASI applications

References

[I] PROFASI: A Monte Carlo simulation package for protein folding and aggregation, A. Irbäck and S. Mohanty, J. Comput. Chem. 27, 1548-1555 (2006)

[II] Folding thermodynamics of peptides, A. Irbäck and S. Mohanty, Biophys. J. 88, 1560-1569 (2005)

[III] Folding of proteins with diverse folds, S. Mohanty and U.H.E. Hansmann, Biophys. J. 91, 3573-3578 (2006)

[IV] Simulation of Top7-CFr: A transient helix extension guides folding, S. Mohanty, J.H. Meinke, O. Zimmermann and U.H.E. Hansmann, Proc. Natl. Acad. Sci. USA, 105, 8004-8007 (2008)

[V] Oligomerization of amyloid $\mathbf{A\beta_{16-22}}$ peptides using hydrogen bonds and hydrophobicity forces, G. Favrin, A. Irbäck and S. Mohanty, Biophys. J. 87, 3657-3664 (2004)

[VI] Structural reorganisation and potential toxicity of oligomeric species formed during the, M. Cheon, I. Chang, S. Mohanty, L.M. Luheshi, C. M. Dobson, M. Vendruscolo and G. Favrin, PLoS Comput. Biol. 3, e173 (2007)

[VII] Spontaneous $\beta$ -barrel formation: An all-atom Monte Carlo study of $\mathbf{A\beta_{16-22}}$ oligomerization, A. Irbäck and S. Mitternacht, Proteins 71, 207-214 (2008)

[VIII] Dissecting the mechanical unfolding of ubiquitin, A. Irbäck, S. Mitternacht and S. Mohanty, Proc. Natl. Acad. Sci. USA 102, 13427-13432 (2005)

[IX] Thermal versus mechanical unfolding of ubiquitin, A. Irbäck and S. Mitternacht, Proteins 65, 759-766 (2006)

[X] Changing the mechanical unfolding pathway of FnIII-10 by tuning the pulling strength, S. Mitternacht, S. Luccioli, A. Torcini, A. Imparato and A. Irbäck, Biophys. J. 96, 429-441 (2009)

[XI] Differences in solution behavior among four semiconductor-binding peptides, S. Mitternacht, S. Schnabel, M. Bachmann, W. Janke and A. Irbäck, J. Phys. Chem. B 111, 4355-4360 (2007)