ILVES: Accurate and Efficient Bond Length and Angle Constraints in Molecular Dynamics

All-atom, force field-based molecular dynamics simulations are essential tools in computational chemistry, enabling the prediction and analysis of biomolecular systems with atomic-level resolution. However, as system sizes and simulation time scales increase, so does the associated computational cost. To extend simulated time using the same resources, a common strategy is to constrain the fastest degrees of freedom, such as bond lengths, allowing for larger integration time steps without compromising accuracy. The de facto state-of-the-art algorithms for this purpose─SHAKE, LINCS, and P-LINCS─are integrated into most molecular dynamics packages and widely adopted across the field. Despite their impact, these methods exhibit limitations: all converge slowly when high numerical accuracy is required, and the LINCS and P-LINCS algorithms cannot handle general angular constraints, limiting further increases in time step. In this article, we introduce ILVES, a family of parallel algorithms that converge so rapidly that it is now practical to solve bond length and associated angular constraint equations as accurately as the hardware will allow. We have integrated ILVES into Gromacs, and our analysis demonstrates that it is superior to the state-of-the-art when constraining bond lengths. Due to its better convergence properties, we also show that if the time step is increased up to 3.5 fs by enforcing angular constraints, ILVES enables a 1.65× increase in simulated time using the same computational resources and wall-clock time, an outcome unattainable with current methods. This advance can significantly reduce the computational cost of most all-atom molecular dynamics simulations while improving their accuracy and extending access to larger systems and longer time scales.

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Publication Details

Journal
Journal of Chemical Theory and Computation
Published
2025-09-04
DOI
https://doi.org/10.1021/acs.jctc.5c01376
Citations
2
Primary Topic
Protein Structure and Dynamics
Type
article
Field-Weighted Citation Impact
1.61

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article

ILVES: Accurate and Efficient Bond Length and Angle Constraints in Molecular Dynamics

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2 citations
Journal of Chemical Theory and Computation
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article

ILVES: Accurate and Efficient Bond Length and Angle Constraints in Molecular Dynamics

Pablo Ibáñez, Juan José Galano‐Frutos, Santiago Marco‐Sola, Carl Christian Kjelgaard Mikkelsen, P. M. Echenique, Maria Cristina De Rosa, Lorién López‐Villellas, Jesús Alastruey-Benedé, Pablo García‐Risueño, Miquel Moretó
article en
2 citations

Abstract

All-atom, force field-based molecular dynamics simulations are essential tools in computational chemistry, enabling the prediction and analysis of biomolecular systems with atomic-level resolution. However, as system sizes and simulation time scales increase, so does the associated computational cost. To extend simulated time using the same resources, a common strategy is to constrain the fastest degrees of freedom, such as bond lengths, allowing for larger integration time steps without compromising accuracy. The de facto state-of-the-art algorithms for this purpose─SHAKE, LINCS, and P-LINCS─are integrated into most molecular dynamics packages and widely adopted across the field. Despite their impact, these methods exhibit limitations: all converge slowly when high numerical accuracy is required, and the LINCS and P-LINCS algorithms cannot handle general angular constraints, limiting further increases in time step. In this article, we introduce ILVES, a family of parallel algorithms that converge so rapidly that it is now practical to solve bond length and associated angular constraint equations as accurately as the hardware will allow. We have integrated ILVES into Gromacs, and our analysis demonstrates that it is superior to the state-of-the-art when constraining bond lengths. Due to its better convergence properties, we also show that if the time step is increased up to 3.5 fs by enforcing angular constraints, ILVES enables a 1.65× increase in simulated time using the same computational resources and wall-clock time, an outcome unattainable with current methods. This advance can significantly reduce the computational cost of most all-atom molecular dynamics simulations while improving their accuracy and extending access to larger systems and longer time scales.

Journal of Chemical Theory and ComputationVol. 21(18)
Universidad de Zaragoza (ES), Barcelona Supercomputing Center (ES), Universidad Peruana de Ciencias e Informática (PE), National Research Council (RO), IDP Ingeniería y Arquitectura Iberia (Spain) (ES), Biocom (US), Instituto de Química Orgánica General (ES), Instituto de Biocomputación y Física de Sistemas Complejos, Umeå University (SE), Universitat Politècnica de Catalunya (ES)
Generalitat de Catalunya, Vetenskapsrådet, Ministerio de Ciencia e Innovación, Umeå Universitet, Barcelona Supercomputing Center, Universidad de Zaragoza, Gobierno de Aragón, Agencia Estatal de Investigación
Openalex Percentile: Top 15%
Protein Structure and Dynamics
1.61
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