This is a fork from the original OTFP code hosted in Cameron Abrams' github.

On the fly parameterization

OTFP computes free-energy surfaces (FES) in MD simulations via temperature-acceleration.

It is written in C and use SWIG to provida a TCL interface to be used with NAMD via TCLforce.

Build system

There is a src/makefile file that can be used to build libraries and executables. It is also posible to compile using meson, e.g.:

git clone https://github.com/alexispaz/otfp.git
cd otfp
meson setup build 
cd build
meson compile -v

Then, to install meson install or to create a distribution meson dist. Default prefix is /usr but can be changed with --prefix, for instance:

meson setup --prefix=$(realpath ./usr) build 

To handle periodicity in FES, Intel Math Kernel Library is required. Intel oneAPI MKL (oneMKL) provides pkg-config metadata files that can be used by meson build system. Check them with:

pkg-config --list-all | grep mkl

The setup will be something like

meson setup --prefix=$(realpath ./usr) -Dblas=mkl-dynamic-lp64-gomp -Dlapack=mkl-dynamic-lp64-gomp build 

To run the examples, set the CFACV_BASEDIR environment variable to the OTFP prefix:

cd examples/OTFP/
export CFACV_BASEDIR=../../usr
./test.sh

Citations

The OTFP method is explained in detail in the original publication:

• Abrams and Vanden-Eijnden. "On-the-fly free energy parameterization via temperature accelerated molecular dynamics." Chem. Phys. Lett., 547 (2012) 114–119. https://doi.org/10.1016/j.cplett.2012.07.064

The extension of OTFP in 2D is explained in:

• Paz, Maragliano, and Abrams. "Effect of Intercalated Water on Potassium Ion Transport through Kv1.2 Channels Studied via On-the-Fly Free-Energy Parametrization." J. Chem. Theory Comput., 14(5) (2018) 2743–2750. https://doi.org/10.1021/acs.jctc.8b00024

The combination of OTFP with Replica Exchanges is described in:

• Paz, Vanden-Eijnden and Abrams. "Polymorphism at 129 dictates metastable conformations of the human prion protein N-terminal β-sheet." Chem. Science, 8(2) (2016) 1225–1232. https://doi.org/10.1039/c6sc03275c

Other publications with OTFP method are:

• Alberini, Paz, Corradi, Abrams, Benfenati and Maragliano. "Molecular Dynamics Simulations of Ion Permeation in human NaV Channels." J. Chem. Theory Comput., 19(10) (2023) 2953–2972. https://doi.org/10.1021/acs.jctc.2c00990

• Paz and Abrams. "Free Energy and Hidden Barriers of the β-Sheet Structure of Prion Protein." J. Chem. Theory Comput., 11(10) (2015) 5024–5034. https://doi.org/10.1021/acs.jctc.5b00576

• Paz and Abrams. "Testing Convergence of Different Free-Energy Methods in a Simple Analytical System with Hidden Barriers." Computation, 6(2) (2018) 27. https://doi.org/10.3390/computation6020027

License

It mantains the same BSD-2-Clause license of the original code at repo.

Original code was developed with support of the National Science Foundation through grant DMR-1207389.

Known issues

In SWIG documentation it is written:

"As a final complication, a major weakness of C++ is that it does not define any sort of standard for binary linking of libraries. This means that C++ code compiled by different compilers will not link together properly as libraries nor is the memory layout of classes and data structures implemented in any kind of portable manner. In a monolithic C++ program, this problem may be unnoticed. However, in Tcl, it is possible for different extension modules to be compiled with different C++ compilers. As long as these modules are self-contained, this probably won't matter. However, if these modules start sharing data, you will need to take steps to avoid segmentation faults and other erratic program behavior. If working with lots of software components, you might want to investigate using a more formal standard such as COM."

Thus, it is recommended to compile OTFP using the same compiler used to compile NAMD.

Another problem that can arise is a segmentation fault when the TCL script of NAMD input loads the compiled cfacv.so shared library. This might be related with differences in the linking of the tcl library in NAMD and in the cfacv.so library. To find which tcl library is using NAMD execute ldd ./namd2. Use that library to compile cfacv.so.

If the tcl library is not found by ldd, it is probably linked static. In that case nm ./namd2 | grep Tcl will show the common symbols defined in the tcl library (e.g. Tcl_AppendResult). This make difficult to known which tcl version was used to compile NAMD. If using the tcl library of the actual system gives segmentation fault, sometimes the issue disappears if the user compile its own TCL library from source and use that one to compile of cfacv.so.

Examples of additional tools to handle chapeau object files

Convert old format of chapeau object files, create converted.ch

./chapconv run12.ch0 

Cropping or expanding the CV space, create croped.ch

./chapcrop cryo.ch 4 18.40076 4 18.40076

Attempt to add chapeau object files

./chapadd croped_*ch

If attempt fail, it might be needed to adjust the size of chapeau objects to have the same number of knots using chapcrop