ILVES

In molecular dynamics, the time step can be incremented through the imposition of constraints on internal degrees of freedom, which raises the total simulated time for equal computational effort. This enables researchers to simulate a wider collection of phenomena of interest, which frequently take place at large time scales. Customarily, bond lengths between pairs of atoms are constrained, although other constraints such as bond angles and dihedral angles can be imposed in order to further increase the time step.

The most popular constraint solvers are SHAKE and LINCS. SHAKE converges locally and linearly and operates serially, limiting parallel performance. LINCS, along with its parallel variant P-LINCS, converges slowly and, in certain cases, fails to converge. Additionally, LINCS is suited only for constraining bond lengths (it fails for coupled constraints on angles). As a result, achieving machine precision solutions with these methods is time-consuming and constraining angles or dihedral angles efficiently remains a challenge.

ILVES is a new algorithm to impose constraints on molecules that solves the same system of differential algebraic equations as SHAKE using Newton's method. ILVES converges quadratically or nearly quadratically and can solve nonlinear constraint equations in parallel, providing faster and more accurate solutions than current (2024) state-of-the-art methods. Notably, ILVES is the first constraint solver to enable applying anglular constraints in parallel.

This repository contains two versions of the ILVES algorithm, integrated into the GROMACS (v2021.0) molecular dynamics package:

• ILVES: The base version, solving the same equations as SHAKE.
• ILVES-FAST: A Quasi-Newton variation that achieves up to twice the performance of ILVES by solving a modified set of equations (reaching the same solution than SHAKE's equations).

Additionally, this repository includes the molecular systems evaluated in the paper "Accurate and Efficient Constrained Molecular Dynamics through Direct Solvers: The ILVES Algorithm."

ILVES in GROMACS

The gromacs-2021 folder contains the 2021.0 version of GROMACS with the addition of the two versions of ILVES. The original P-LINCS solver has been modified to allow users to set a custom tolerance for the algorithm, identically to SHAKE's shake-tol parameter in the .mdp file. To reach the chosen tolerance, P-LINCS' repeats its correction phase, controlled by the lincs-iter parameter in the original implementation, until the desired error is met.

Installation

To install GROMACS with ILVES, follow the standard GROMACS installation guide. ILVES functionality will be available out of the box.

Note: It’s recommended to compile with GCC v10 as later versions may cause compilation errors in parts of the package.

Example of an MPI/OpenMP installation in double-precision mode:

mkdir build
cd build

cmake ../gromacs-2021 \
-DGMX_BUILD_OWN_FFTW=on \
-DGMX_MPI=on \
-DGMX_DOUBLE=on \
-DCMAKE_BUILD_TYPE=Release \
-DREGRESSIONTEST_DOWNLOAD=off \
-DBUILD_TESTING=off \
-DGMX_GPU=off \
-DGMX_OPENMP=on \
-DGMX_X11=off \
-DGMXAPI=off

make
make install

Usage

To use ILVES as the constraint solver in your simulation, specify the following parameters in the .mdp file:

constraint-algorithm=ilves  ; Use ILVES
; OR
constraint-algorithm=ilvesf ; Use ILVES-FAST
ilves-tol=0.0001            ; Relative tolerance for ILVES, analogous to shake-tol in SHAKE.
ilves-mpi-neigh=4"          ; With domain decomposition, the cell size is limited by the distance spanned by ilves-mpi-neigh+1 constraints, similar to lincs-order.

Our modified version of P-LINCS introduces changes to the algorithm's parameters:

lincs-tol=0.0001  ; Relative tolerance for LINCS, analogous to shake-tol and ilves-tol. This is a new parameter.
lincs-iter=100    ; Maximum allowed iterations in the LINCS correction phase (fixed number of iterations in the original P-LINCS).

Reproduce our Results

The simulations folder includes the molecular systems evaluated in the ILVES manuscript (2025). Additionally, it provides scripts to generate necessary files for each system's production run, along with a script to perform production runs with different tolerances, parallel configurations, and constraint solvers.

• simulations/setup.sh: Sets up the environment for running our simulations.
• simulations/ffs: Contains the force fields used in our simulations.
• simulations/systems: Contains a subfolder for each molecular system studied. Each system folder includes a setup script, directories with required input files (e.g., .mdp and .pdb files) for simulation preparation, and automation scripts for generating production-ready files. Additionally, the files-for-prod folder provides pre-generated input files for immediate use in production runs.
• simulations/prod_run.sh: Executes production runs with various tolerances, parallel configurations, and constraint solvers using the generated production files.

Generating Production Files for a System

Each system folder includes a sequence of scripts, numbered from 1 to N, to automatically generate the required production files:

cd simulations
source setup.sh

cd systems/DESIRED_SYSTEM
source setup.sh

bash 1_ONE_SCRIPT
...
bash N_extract_prod_files.sh #  The files-for-prod folder will contain all required files for a production run.

You may skip the setup and directly use the pre-generated files in files-for-prod.

Running a Production Simulation

To execute a production run, you can use simulations/prod_run.sh, which automates .tpr file generation for various tolerances, parallel setups, and solvers. Check out the script to verify which simulations it will execute. Run the script as follows:

source ./simulations/setup.sh
source ./simulations/systems/DESIRED_SYSTEM/setup.sh

bash prod_run.sh

Cite Us

Lorién López-Villellas, Carl Christian Kjelgaard Mikkelsen, Juan José Galano-Frutos, Santiago Marco-Sola, Jesús Alastruey-Benedé, Pablo Ibáñez, Miquel Moretó, Maria Cristina De Rosa, and Pablo García-Risueño. ILVES: Accurate and Efficient Bond Length and Angle Constraints in Molecular Dynamics, Journal of Chemical Theory and Computation, 2025.

@article{LpezVillellas2025,
  title = {ILVES: Accurate and Efficient Bond Length and Angle Constraints in Molecular Dynamics},
  volume = {21},
  ISSN = {1549-9626},
  url = {http://dx.doi.org/10.1021/acs.jctc.5c01376},
  DOI = {10.1021/acs.jctc.5c01376},
  number = {18},
  journal = {Journal of Chemical Theory and Computation},
  publisher = {American Chemical Society (ACS)},
  author = {López-Villellas,  Lorién and Mikkelsen,  Carl Christian Kjelgaard and Galano-Frutos,  Juan José and Marco-Sola,  Santiago and Alastruey-Benedé,  Jesús and Ibáñez,  Pablo and Echenique,  Pablo and Moretó,  Miquel and De Rosa,  Maria Cristina and García-Risueño,  Pablo},
  year = {2025},
  month = sep,
  pages = {8711–8719}
}