In-House Software

Software for proton and/or electron titration using a single protein structure

meadTools [download]: This is a set of software tools useful to run binding simulations of electrons and protons [Baptista 1999, Teixeira 2002], using proton tautomers [Baptista 2001, Teixeira 2002] or not, based on Poisson-Boltzmann (PB) calculations. It can be used to create the input to PETIT or MCRP (see below), assuming that the PB calculations are done using the MEAD package by Donald Bashford. Some tools depend also on GROMACS and ASC. (Since the original link for MEAD seems to be down, and since the program is distributed with a GPL, we provide here its tar file.)

PETIT [download]: General program for systems with multiple-state sites. The typical use of the program is the treatment of proton configurations [Baptista 2001, Teixeira 2002], which includes the protonation of sites with proton tautomerism, and the orientation of hydroxyl and thiol groups (Ser, Thr, Cys) and water molecules. (Note that PETIT can be used outside of the context of protonation and/or redox equilibrium, such as to perform conformational sampling of side-chain conformations, but in such a case the required structural energy terms cannot be obtained using meadTools.)
MCRP [download]: This program is intended for systems with two-state sites only [Baptista 1999]. It is much faster than PETIT in this particular case, because extensive optimizations can be done.

Software for constant-pH molecular dynamics

ST-CpHMD-v4.1.2_GMX2018 : Stochastic titration method for GROMACS 2018 [download]: This package implements the stochastic titration method developed by Baptista and co-workers [Baptista 2002, Machuqueiro 2006, Machuqueiro 2011] to perform constant-pH molecular dynamics simulations.

ST-CpHMD-v4.1_GMX4.07 : Stochastic titration method for GROMACS 4.0.7 [download]: This package implements the stochastic titration method developed by Baptista and co-workers [Baptista 2002, Machuqueiro 2006, Machuqueiro 2011] to perform constant-pH molecular dynamics simulations.

Software to use with GROMACS

GROMACS using GRF with ionic strength as an external parameter [download for GROMACS 4.0.7] [download for GROMACS 2018.3]: The implementation of the generalized reaction field (GRF) method [Tironi 1995] in GROMACS uses the charges of the system to automatically determine an ionic strength value that is used by the method. We have introduced a simple modification in GROMACS [Machuqueiro 2006] that takes instead the ionic strength as an external parameter given in the .mdp file, like the temperature or the pressure.

Fix_topology : a program to fix GROMACS topologies [download]: This program was primarily developed to fix the bonds, angles and proper dihedrals that are left "empty" (i.e., without parameters) in a GROMACS topology file upon the creation of special bonds (specbonds).

grms_to_central : gets central structure from RMSD data [download]: This program reads the binary output of the GROMACS analysis tool g_rms (or 'gmx rms' in recent versions), which is produced with the option -bin, and calculates the central structure as defined in [Campos 2009].

Analysis Software

LandscapeTools : Tool to analyse density and energy landscapes [download]: This package reads a set of points in space and computes the probability density and corresponding free energy in that space, identifying the resulting energy basins and the transitions between them [Campos 2009].

FixBox : Tool to fix MD simulation boxes [download]
This program reads a molecular structure in GRO format (single or trajectory) and reassembles a multi-molecular complex "broken" by periodic boundary conditions. [Baptista 2022]

For help or bug reporting, contact us at cphmd@itqb.unl.pt.

References

Baptista, A. M., Martel, P. J., Petersen, S. B. (1997) Simulation of protein conformational freedom as a function of pH: constant-pH molecular dynamics using implicit titration. Proteins, 27:523-544.

Baptista, A. M., Martel, P. J., Soares, C. M. (1999) Simulation of electron-proton coupling with a Monte Carlo method: Application to cytochrome c₃ using continuum electrostatics. Biophys. J. 76:2978-2998.

Baptista, A. M., Soares, C. M. (2001) Some theoretical and computational aspects of the inclusion of proton isomerism in the protonation equilibrium of proteins. J. Phys. Chem. B, 105:293-309.

Baptista, A. M., Teixeira, V. H., Soares, C. M. (2002) Constant-pH molecular dynamics using stochastic titration. J. Chem. Phys. 117:4184-4200.

Baptista, A. M., Campos, da Rocha, L., S. R. R. (2022) FixBox: A General Algorithm to Fix Molecular Systems in Periodic Boxes. J. Chem. Inf. Model. 62:4435. https://doi.org/10.1021/acs.jcim.2c00823

Campos, S. R. R., Baptista, A. M. (2009) Conformational analysis in a multidimensional energy landscape: study of an arginylglutamate repeat. J. Phys. Chem. B, 113:15989-16001.

Machuqueiro, M., Baptista, A. M. (2006) Constant-pH molecular dynamics with ionic strength effects: protonation-conformation coupling in decalysine. J. Phys. Chem. B, 110:2927-2933.

Machuqueiro, M., Baptista, A. M. (2011) Is the prediction of pKa values by constant-pH molecular dynamics being hindered by inherited problems? Proteins Struct. Funct. Bioinf., 79:3437–3447.

Teixeira, V. H., Soares, C. M., Baptista, A. M. (2002) Studies of the reduction and protonation behavior of tetraheme cytochromes using atomic detail. J. Biol. Inorg. Chem. 7:200-216.

Tironi, I. G., Sperb, R., Smith, P. E., van Gunsteren, W. F. (1995) A generalized reaction field method for molecular-dynamics simulations. J. Chem. Phys. 102:5451-5459.