Hippo

From Biowerkzeug Wiki

A peptide folds and inserts into a membrane; the membrane is represented by an implicit Generalized Born model.

Hippo is a software package for simulation and analysis of bio-molecules at an atomic level. It has been specifically developed for very efficient protein folding studies in aqueous and membrane environments. The code is very fast due to optimized and hand-coded assembly routines which make use of fast multi-media instructions on modern x86 cpus. Hippo is (partially) parallelized (using industry-standard OpenMP).

Features

Not this hippo.

Simulation methods

• Molecular dynamics (MD) in NVT, NPT, NVE ensembles [1]
• Metropolis Monte Carlo (MC) in NVT and NPT ensembles [2, 3]
• Replica exchange with MD and MC [4]

Force fields

• OPLS-AA [5, 6]

Solvation models

• explicit solvent (water: TIP4P [7], SPC [8])
• Generalized Born implicit solvent (GB/SA)
• Generalized Born implicit membrane (GB/IM) [1, 4, 9, 10]

Enhanced productivity

A number of features make it easy to use Hippo so that one can spend more time on working on problems and less time on setting up structures or dealing with system crashes:

• seamless restarts
• intelligent pdb structure loader: reads most pdbs, can complete missing atoms, and builds the topology
• graphical frontend under development (Windows only)

Analysis

Adiabatic Generalized Born energy surface for different positions and orientations of a helical peptide in a membrane (output from the translation+rotation energy scan analysis tool).

A growing number of analysis tools are built into Hippo, for instance

adiabatic translation+rotation energy scan

determines the Generalized Born energy of a peptide in a membrane [11, 12]; this allows to decide if a (typically helical) peptide inserts into the membrane and at which depth and angle or if it prefers a surface-bound or even a fully solvated state

RMSD

calculates the root mean square deviation of trajectory frames to a reference structure

helicity

degree of helicity of segments along trajectory

Z - tilt - kink graph

Calculates center of mass, tilt angle, and kink angle of a peptide in a membrane as a function of simulation time. The membrane is in the xy plane, with z = 0 the membrane center. Kink angle is with respect to the membrane normal. [13]

cluster

Performs a cluster analysis using the pairwise method by Daura et al.[14]

fit to phase

recenters trajectory on the centre of mass of a phase (such as a lipid membrane)

fit solute to previous frames

Generate a PDB movie by RMSD fitting the solute of each frame to the previous frame.

The Hippo output format is a binary xyz-movie (see the definition of the xyz format); thus many other analysis tools can also be used.

Installation

Download

Binaries are publicly available from the Biowerkzeg.com download page for Linux and Windows.

Installing the software

Unzip the downloaded file. It will unpack into its own hippo directory where you will find

• compiled executables (see below)
  • hippo: the MD and MC program
  • analyse: the analysis program
• the manual (pdf)
• the license (to which you consent by downloading)
• the OPLS-AA forcefield file (in Hippo format)
• the readme.txt file
• the testjobs directory with example systems

The package includes binaries that run under Linux and Windows on any Intel or AMD processor that has the SSE or SSSE3 multi media instructions. Depending on your system and needs, choose an executable from the package as shown in the table Hippo executables.

If in doubt, simply try them out in order; if it will not run you will receive an error message such as

Fatal Error: This program was not built to run on the processor in your system.
The allowed processors are: Intel(R) Core(TM) Duo processors and compatible Intel processors 
with supplemental Streaming SIMD Extensions 3 (SSSE3) instruction support.

In this case try the hippo_p3 or hippo_p3.exe executable. If this still doesn't work, post a request in the Hippo Installation forum.

Executables with the _mpi extension have been compiled with MPI support (mpich2) and are only used for replica exchange simulations (REXMD). If you just want to run multithreaded simulations just use the standard binaries (which are all compiled with OpenMP).

Test cases

The testjobs directory contains a number of testcases.

Run the calc_testjobs_linux.bat or calc_testjobs_win32.bat script in order to perform all tests. On modern processors this should take between 2 and 4 Minutes.

Use the tests in order to get started in running your own systems.

References

1. Jakob P. Ulmschneider and Martin B. Ulmschneider. Sampling efficiency in explicit and implicit membrane environments studied by peptide folding simulations. Proteins 10.1002/prot.22270. [Proteins2008]
2. Ulmschneider JP and Jorgensen WL. Polypeptide folding using Monte Carlo sampling, concerted rotation, and continuum solvation. J Am Chem Soc 2004 Feb 18; 126(6) 1849-57. doi:10.1021/ja0378862 pmid:14871118. PubMed HubMed [JACS2004]
3. Ulmschneider JP, Ulmschneider MB, and Di Nola A. Monte Carlo vs molecular dynamics for all-atom polypeptide folding simulations. J Phys Chem B 2006 Aug 24; 110(33) 16733-42. doi:10.1021/jp061619b pmid:16913813. PubMed HubMed [JPhysChemB2006]
4. Ulmschneider JP, Ulmschneider MB, and Di Nola A. Monte Carlo folding of trans-membrane helical peptides in an implicit generalized Born membrane. Proteins 2007 Nov 1; 69(2) 297-308. doi:10.1002/prot.21519 pmid:17600830. PubMed HubMed [Proteins2007]
5. W. L. Jorgensen, D. S. Maxwell, and J. Tirado-Rives. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc., 118(45):11225–11236, 1996. 10.1021/ja9621760.

   [Jorgensen1996]

6. George A. Kaminski, Richard A. Friesner, Julian Tirado-Rives, and William L. Jorgensen. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B, 105(28):6474–6487, 2001. 10.1021/jp003919d.

   [Kaminski2001]

7. W. L. Jorgensen and J. D. Madura. Temperature and size dependence for Monte-Carlo simulations of TIP4P water. Mol. Phys., 56(6):1381–1392, December 1985.

   [Jorgensen1985]

8. H. J. C. Berendsen, J. P. M. Postma, W. F. van Gunsteren, and J. Hermans. Interaction models for water in relation to protein hydration. In B. Pullman, editor, Intermolecular Forces, page 331. D. Reidel Publishing Company, Dordrecht, Holland, 1981.

   [Berendsen1981]

9. Ulmschneider MB, Ulmschneider JP, Sansom MS, and Di Nola A. A generalized born implicit-membrane representation compared to experimental insertion free energies. Biophys J 2007 Apr 1; 92(7) 2338-49. doi:10.1529/biophysj.106.081810 pmid:17218457. PubMed HubMed [BJ2007]
10. Ulmschneider MB, Sansom MS, and Di Nola A. Properties of integral membrane protein structures: derivation of an implicit membrane potential. Proteins 2005 May 1; 59(2) 252-65. doi:10.1002/prot.20334 pmid:15723347. PubMed HubMed [Proteins2005]
11. Ulmschneider MB and Ulmschneider JP. Membrane adsorption, folding, insertion and translocation of synthetic trans-membrane peptides. Mol Membr Biol 2008 Apr; 25(3) 245-57. doi:10.1080/09687680802020313 pmid:18428040. PubMed HubMed [MMB2008]
12. Ulmschneider MB, Sansom MS, and Di Nola A. Evaluating tilt angles of membrane-associated helices: comparison of computational and NMR techniques. Biophys J 2006 Mar 1; 90(5) 1650-60. doi:10.1529/biophysj.105.065367 pmid:16339877. PubMed HubMed [BJ2006]
13. Cordes FS, Bright JN, and Sansom MS. Proline-induced distortions of transmembrane helices. J Mol Biol 2002 Nov 8; 323(5) 951-60. pmid:12417206. PubMed HubMed [Cordes2002]
14. X Daura, K Gademann, B Jaun, D Seebach, WF van Gunsteren, and AE Mark. Peptide folding: When simulation meets experiment. Angewandte Chemie-International Edition, 38 (1-2):236–240, 1999. 10.1002/(SICI)1521-3773(19990115)38:1/2<236::AID-ANIE236>3.0.CO;2-M.

    [Daura1999]