A hacked, hardwired GROMACS-4.5.5 that runs mABP, well-tempered metadynamics, μ-tempered metadynamics, or a SHUS-based tempered metadynamics for alanine dipeptide. While the name might not stick, you can find out about μ-tempering on the arxiv.

This code is modified for the following functions:

• Compute Phi-Psi free energy via mABP

• Compute Phi-Psi free energy via well-tempered or μ-tempered metadynamics

• Compute Phi-Psi free energy via an alternate tempered metadynamics

This is not standard gromacs, don't use it for anything outside of alanine dipeptide unless you modify md.c and hellof.f to match your application!

The biasing code can be found here. There are comments and the code is easy to read if you can stomach going back to 1985. You wont need a DeLorean.

All the things required for building simulation inputs are also included in the ALANINEsystem subdirectory.

1. Go to the ABPenabledGROMACS directory.

2. Run the ./configure command with whatever options you need to use. Use --prefix=PATH-TO-YOUR-ABPenabledGROMACS to install the executable to the location expected by the Run-mABP/ Run-WTmetaD/ Run-Mu/ and Run-SHUSish directories.

3. Run make clean

4. cd to src/kernel and compile hello.f with gfortran -O3 -fbounds-check -c hello.f The file hello.f is a fortran routine written very transparently so that each method can be cleanly compared to the other.

5. Edit src/kernel/Makefile as follows:

• Line 144 should read: md_openmm.$(OBJEXT) hello.o
• Line 232 should read: LIBS = -lnsl -lm -lgfortran

6. Run make install from the ABPenabledGROMACS directory

1. Go to ABPenabledGROMACS/ALANINEsystem and build a new tpr file:

• ../bin/grompp -f md.mdp -c isob.gro -t isob.cpt -o ala.tpr

2. Copy this ala.tpr file into the run directories: Run-mABP Run-WTmetaD Run-Mu Run-SHUSish and edit the params.in file to your liking

3. Simulations can be launched within these run directories with ./mdrun -v -deffnm ala

4. You can adjust the parameters and see how things change.

1. The simulations will write a file named "freeE" that contains the current free energy estimate. The Phi-Psi angles are given in the first two columns, the free energy estimate is given in the third column.

2. Simulations also write a file named "fort.88" The first column is timestep, second and third columns are collective variables (angles), the fourth column is the convergence metric (equation 28 in the paper)