xBFreE in a nutshell¶

xBFreE implements all the features in gmx_MMPBSA with support for GROMACS, AMBER, NAMD, and CHARMM. So far, this includes the PB and other implicit solvent-based methods for calculating binding free energies. We intend to implement several more methods, such as LIE, FEP, TI, etc. in the future.

xBFreE general workflow¶

flowchart TB
    a1[xbfree]
    subgraph MMPBSA
    direction TB
        m1{{gmx_MMPBSA}}
        m2{{amber_MMPBSA}}
        m3{{namd_MMPBSA}}
        m4{{charmm_MMPBSA}}
    end
    a1 --> m1
    a1 --> m2
    a1 --> m3
    a1 --> m4

    m1 --> f1[Calculation]
    m2 --> f1
    m3 --> f1
    m4 --> f1
    f1 --> g1[Results]

Types of calculations you can do¶

There are many options available in xBFreE. These are some calculations you can perform with xBFreE:

MMPBSA calculations¶

• Normal binding free energies, with either PB, GB or 3D-RISM solvent models. Each can be done with either 1, 2, or 3 different trajectories. The complex trajectory must always be provided. Whichever trajectories of the receptor and/or ligand that are NOT specified will be extracted from that of the complex. This allows a 1-, 2-, or 3-trajectory analysis. All PB calculations and GB models are performed via the sander program. Calculations with 3D-RISM solvent model are performed with rism3d.snglpnt built with AmberTools.
• Stability calculations with any solvent model (i.e PB, GB or 3D-RISM).
• Alanine scanning with either PB or GB implicit solvent models. All trajectories will be mutated to match the mutated topology files, and whichever calculations that would be carried out for the normal systems are also carried out for the mutated systems. Note that only 1 mutation is allowed per simulation, and it must be to an alanine or glycine. If mutant_only variable is not set to 1, differences resulting from the mutations are calculated.
• Entropy corrections. An entropy term can be added to the free energies calculated above using either the quasi-harmonic, the normal mode, interaction entropy or C2 approximations. Calculations will be performed for the normal and mutated systems (alanine scanning) as requested. Normal mode calculations are done with the mmpbsa_py_nabnmode program included with AmberTools.
• Decomposition schemes. The energy terms will be decomposed according to the decomposition scheme (per-residue or per-wise) outlined in the idecomp variable description. This should work with all the above, though entropy terms cannot be decomposed.
• QM/MMGBSA. This is a binding free energy (or stability calculation) using the Generalized Born solvent model allowing you to treat part of your system with a quantum mechanical Hamiltonian.
• Support for Membrane Proteins. Calculate the MMPBSA binding free energy for a ligand bound to a protein that is embedded into a membrane. In this case, the membrane is implemented as a slab-like region with a uniform or heterogeneous dielectric constant depth profile.

LIE calculations¶

Coming soon!

FEP calculations¶

Coming soon!

TI calculations¶

Coming soon!

xBFreE a technical view¶

xBFreE is a python module that contains 2 applications:

• xbfree is the fundamental application and carries out all the calculations mentioned above
• xbfree-test is a tool designed to test if the installation was successful by running one or more available examples in xBFreE.

• xbfree-analyzer provides an intuitive way to analyze the data from xBFreE calculations and save high-quality images