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bioRxiv · 10.1101/2025.07.21.665906

multiSMD - a Python toolset for multidirectional Steered Molecular Dynamics

Walczewska-Szewc, K.·Niklas, B.·Nowak, W.
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Abstract

Understanding the direction-dependence of molecular interactions is critical for elucidating biological processes such as protein-protein binding, ligand dissociation, and mechanotransduction. While steered molecular dynamics (SMD) simulations enable the study of force-induced transitions, conventional single-direction approaches may overlook anisotropic responses inherent to biomolecular systems. Here, we present multiSMD, a Python-based tool that automates the setup and analysis of multi-directional SMD simulations in NAMD and GROMACS. By systematically probing forces along multiple spatial vectors, multiSMD captures direction-dependent phenomena--such as varying energy barriers or structural resilience--that remain hidden in traditional SMD. We demonstrate the utility of our approach through three distinct applications: (i) anisotropic unbinding in a protein-protein interaction, (ii) ligand dissociation pathways dependent on pulling direction, and (iii) force-induced remodeling of intrinsically disordered regions. multiSMD streamlines the exploration of mechanical anisotropy in biomolecules, offering a computational framework to guide experiments (e.g., AFM or optical tweezers) and uncover mechanistic insights inaccessible to single-axis methods. Availability and implementation: multiSMD is freely available at https://github.com/kszewc/multiSMD

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Walczewska-Szewc, K., Niklas, B., Nowak, W.. 2025-07-24. multiSMD - a Python toolset for multidirectional Steered Molecular Dynamics. https://doi.org/10.1101/2025.07.21.665906

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