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Hauptverfasser: Müllender, Lukas, Rizzi, Andrea, Parrinello, Michele, Carloni, Paolo, Mandelli, Davide
Format: Preprint
Veröffentlicht: 2023
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Online-Zugang:https://arxiv.org/abs/2311.05571
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author Müllender, Lukas
Rizzi, Andrea
Parrinello, Michele
Carloni, Paolo
Mandelli, Davide
author_facet Müllender, Lukas
Rizzi, Andrea
Parrinello, Michele
Carloni, Paolo
Mandelli, Davide
contents A variety of enhanced sampling methods predict multidimensional free energy landscapes associated with biological and other molecular processes as a function of a few selected collective variables (CVs). The accuracy of these methods is crucially dependent on the ability of the chosen CVs to capture the relevant slow degrees of freedom of the system. For complex processes, finding such CVs is the real challenge. Machine learning (ML) CVs offer, in principle, a solution to handle this problem. However, these methods rely on the availability of high-quality datasets -- ideally incorporating information about physical pathways and transition states -- which are difficult to access, therefore greatly limiting their domain of application. Here, we demonstrate how these datasets can be generated by means of enhanced sampling simulations in trajectory space via the metadynamics of paths [arXiv:2002.09281] algorithm. The approach is expected to provide a general and efficient way to generate efficient ML-based CVs for the fast prediction of free energy landscapes in enhanced sampling simulations. We demonstrate our approach with two numerical examples, a two-dimensional model potential and the isomerization of alanine dipeptide, using deep targeted discriminant analysis as our ML-based CV of choice.
format Preprint
id arxiv_https___arxiv_org_abs_2311_05571
institution arXiv
publishDate 2023
record_format arxiv
spellingShingle Effective Data-Driven Collective Variables for Free Energy Calculations from Metadynamics of Paths
Müllender, Lukas
Rizzi, Andrea
Parrinello, Michele
Carloni, Paolo
Mandelli, Davide
Computational Physics
A variety of enhanced sampling methods predict multidimensional free energy landscapes associated with biological and other molecular processes as a function of a few selected collective variables (CVs). The accuracy of these methods is crucially dependent on the ability of the chosen CVs to capture the relevant slow degrees of freedom of the system. For complex processes, finding such CVs is the real challenge. Machine learning (ML) CVs offer, in principle, a solution to handle this problem. However, these methods rely on the availability of high-quality datasets -- ideally incorporating information about physical pathways and transition states -- which are difficult to access, therefore greatly limiting their domain of application. Here, we demonstrate how these datasets can be generated by means of enhanced sampling simulations in trajectory space via the metadynamics of paths [arXiv:2002.09281] algorithm. The approach is expected to provide a general and efficient way to generate efficient ML-based CVs for the fast prediction of free energy landscapes in enhanced sampling simulations. We demonstrate our approach with two numerical examples, a two-dimensional model potential and the isomerization of alanine dipeptide, using deep targeted discriminant analysis as our ML-based CV of choice.
title Effective Data-Driven Collective Variables for Free Energy Calculations from Metadynamics of Paths
topic Computational Physics
url https://arxiv.org/abs/2311.05571