arXiv subjects

Luca Donati

Publications and source records attributed to Luca Donati.

15 recordsLinked to original sources

arXiv2026

Effective Dynamics and Transition Pathways from Koopman-Inspired Neural Learning of Collective Variables

The ISOKANN (Invariant Subspaces of Koopman Operators Learned by Artificial Neural Networks) framework provides a data-driven route to extract collective variables (CVs) and effective dynamics from complex molecular systems. In this work, we integrate the theoretical foundation of Koopman operators with Krylov-like subspace algorithms, and reduced dynamical modeling to build a coherent picture of how to describe metastable transitions in high-dimensional systems based on CVs. Starting from the identification of CVs based on dominant invariant subspaces, we derive the corresponding effective dynamics on the latent space and connect these to transition rates and times, committor functions, and transition pathways. The combination of Koopman-based learning and reduced-dimensional effective dynamics yields a principled framework for computing transition rates and pathways from simulation data. Numerical experiments on one-, two-, and three-dimensional benchmark potentials illustrate the ability of ISOKANN to reconstruct the coarse-grained kinetics and reproduce transition times across enthalpic and entropic barriers.

math.DS↗

arXiv2024

Topological analysis reveals multiple pathways in molecular dynamics

Molecular Dynamics simulations are essential tools for understanding the dynamic behavior of biomolecules, yet extracting meaningful molecular pathways from these simulations remains challenging due to the vast amount of generated data. In this work, we present Molecular Kinetics via Topology (MoKiTo), a novel approach that combines the ISOKANN algorithm to determine the reaction coordinate of a molecular system with a topological analysis inspired by the Mapper algorithm. Our strategy efficiently identifies and characterizes distinct molecular pathways, enabling the detection and visualization of critical conformational transitions and rare events. This method offers deeper insights into molecular mechanisms, facilitating the design of targeted interventions in drug discovery and protein engineering.

physics.chem-ph↗

arXiv2024

The Kramers turnover in terms of a macro-state projection on phase space

We have investigated how Langevin dynamics is affected by the friction coefficient using the novel algorithm ISOKANN, which combines the transfer operator approach with modern machine learning techniques. ISOKANN describes the dynamics in terms of an invariant subspace projection of the Koopman operator defined in the entire state space, avoiding approximations due to dimensionality reduction and discretization. Our results are consistent with the Kramers turnover and show that in the low and moderate friction regimes, metastable macro-states and transition rates are defined in phase space, not only in position space.

physics.chem-ph↗

arXiv2023

Accuracy of reaction coordinate based rate theories for modelling chemical reactions: insights from the thermal isomerization in retinal

Modern potential energy surfaces have shifted attention to molecular simulations of chemical reactions. While various methods can estimate rate constants for conformational transitions in molecular dynamics simulations, their applicability to studying chemical reactions remains uncertain due to the high and sharp energy barriers and complex reaction coordinates involved. This study focuses on the thermal cis-trans isomerization in retinal, employing molecular simulations and comparing rate constant estimates based on one-dimensional rate theories with those based on sampling transitions and grid-based models for low-dimensional collective variable spaces. Even though each individual method to estimate the rate passes its quality tests, the rate constant estimates exhibit disparities of up to four orders of magnitude. Rate constant estimates based on one-dimensional reaction coordinates prove challenging to converge, even if the reaction coordinate is optimized. However, consistent estimates of the rate constant are achieved by sampling transitions and by multi-dimensional grid-based models.

physics.chem-ph↗

arXiv2023

Tensor-SqRA: Modeling the Transition Rates of Interacting Molecular Systems in terms of Potential Energies

Estimating the rate of rare conformational changes in molecular systems is one of the goals of Molecular Dynamics simulations. In the past decades, a lot of progress has been done in data-based approaches towards this problem. In contrast, model-based methods such as the Square Root Approximation (SqRA), directly derive these quantities from the potential energy functions. In this article we demonstrate how the SqRA formalism naturally blends with the tensor structure obtained by coupling multiple systems, resulting in the tensor-based Square Root Approximation (tSqRA). It enables efficient treatment of high-dimensional systems using the SqRA and provides an algebraic expression of the impact of coupling energies between molecular subsystems. Based on the tSqRA, we also develop the Projected Rate Estimation (PRE), a hybrid data-model-based algorithm that efficiently estimates the slowest rates for coupled systems. In addition, we investigate the possibility of integrating low-rank approximations within this framework to maximize the potential of the tSqRA.

physics.chem-ph↗

arXiv2023

Efficient Estimation of Transition Rates as Functions of pH

Extracting the kinetic properties of a system whose dynamics depend on the pH of the environment with which it exchanges energy and atoms requires sampling the Grand Canonical Ensemble. As an alternative, we present a novel strategy that requires simulating only the most recurrent Canonical Ensembles that compose the Grand Canonical Ensemble. The simulations are used to estimate the Gran Canonical distribution for a specific pH value by reweighting and to construct the transition rate matrix by discretizing the Fokker-Planck equation by Square Root Approximation and robust Perron Cluster Cluster Analysis. As an application, we have studied the tripeptide Ala-Asp-Ala.

physics.chem-ph↗

arXiv2022

A review of Girsanov Reweighting and of Square Root Approximation for building molecular Markov State Models

Dynamical reweighting methods permit to estimate kinetic observables of a stochastic process governed by a target potential $\tilde{V}(x)$ from trajectories that have been generated at a different potential $V(x)$. In this article, we present Girsanov reweighting and Square Root Approximation (SqRA): the first method reweights path probabilities exploiting the Girsanov theorem and can be applied to Markov State Models (MSMs) to reweight transition probabilities; the second method was originally developed to discretize the Fokker-Planck operator into a transition rate matrix, but here we implement it into a reweighting scheme for transition rates. We begin by reviewing the theoretical background of the methods, then present two applications relevant to Molecular Dynamics (MD), highlighting their strengths and weaknesses.

physics.chem-ph↗

arXiv2022

Assessing transition rates as functions of environmental variables

We present a method to estimate the transition rates of molecular systems under different environmental conditions which cause the formation or the breaking of bonds and require the sampling of the Grand Canonical Ensemble. For this purpose, we model the molecular system in terms of probable "scenarios", governed by different potential energy functions, which are separately sampled by classical MD simulations. Reweighting the canonical distribution of each scenario according to specific environmental variables, we estimate the grand canonical distribution, then we use the Square Root Approximation (SqRA) method to discretize the Fokker-Planck operator into a rate matrix and the robust Perron Cluster Cluster Analysis (PCCA+) method to coarse-grain the kinetic model. This permits to efficiently estimate the transition rates of conformational states as functions of environmental variables, for example, the local pH at a cell membrane. In this work we formalize the theoretical framework of the procedure and we present a numerical experiment comparing the results with those provided by a constant-pH method based on non-equilibrium Molecular Dynamics Monte Carlo simulations. The method is relevant for the development of new drug design strategies which take into account how the cellular environment influences biochemical processes.

physics.chem-ph↗

arXiv2021

Transferring Knowledge with Attention Distillation for Multi-Domain Image-to-Image Translation

Gradient-based attention modeling has been used widely as a way to visualize and understand convolutional neural networks. However, exploiting these visual explanations during the training of generative adversarial networks (GANs) is an unexplored area in computer vision research. Indeed, we argue that this kind of information can be used to influence GANs training in a positive way. For this reason, in this paper, it is shown how gradient based attentions can be used as knowledge to be conveyed in a teacher-student paradigm for multi-domain image-to-image translation tasks in order to improve the results of the student architecture. Further, it is demonstrated how "pseudo"-attentions can also be employed during training when teacher and student networks are trained on different domains which share some similarities. The approach is validated on multi-domain facial attributes transfer and human expression synthesis showing both qualitative and quantitative results.

cs.CV↗

arXiv2020

Markov models from the Square Root Approximation of the Fokker-Planck equation: calculating the grid-dependent flux

Molecular dynamics are extremely complex, yet understanding the slow components of their dynamics is essential to understanding their macroscopic properties. To achieve this, one models the molecular dynamics as a stochastic process and analyses the dominant eigenfunctions of the associated Fokker-Planck operator, or of closely related transfer operators. So far, the calculation of the discretized operators requires extensive molecular dynamics simulations. The Square-root approximation of the Fokker-Planck equation is a method to calculate transition rates as a ratio of the Boltzmann densities of neighboring grid cells times a flux, and can in principle be calculated without a simulation. In a previous work we still used molecular dynamics simulations to determine the flux. Here, we propose several methods to calculate the exact or approximate flux for various grid types, and thus estimate the rate matrix without a simulation. Using model potentials we test computational efficiency of the methods, and the accuracy with which they reproduce the dominant eigenfunctions and eigenvalues. For these model potentials, rate matrices with up to $\mathcal{O}(10^6)$ states can be obtained within seconds on a single high-performance compute server if regular grids are used.

physics.chem-ph↗

arXiv2020

MetalGAN: Multi-Domain Label-Less Image Synthesis Using cGANs and Meta-Learning

Image synthesis is currently one of the most addressed image processing topic in computer vision and deep learning fields of study. Researchers have tackled this problem focusing their efforts on its several challenging problems, e.g. image quality and size, domain and pose changing, architecture of the networks, and so on. Above all, producing images belonging to different domains by using a single architecture is a very relevant goal for image generation. In fact, a single multi-domain network would allow greater flexibility and robustness in the image synthesis task than other approaches. This paper proposes a novel architecture and a training algorithm, which are able to produce multi-domain outputs using a single network. A small portion of a dataset is intentionally used, and there are no hard-coded labels (or classes). This is achieved by combining a conditional Generative Adversarial Network (cGAN) for image generation and a Meta-Learning algorithm for domain switch, and we called our approach MetalGAN. The approach has proved to be appropriate for solving the multi-domain problem and it is validated on facial attribute transfer, using CelebA dataset.

cs.LG↗

arXiv2019

Dynamical reweighting methods for Markov models

Markov State Models (MSM) are widely used to elucidate dynamic properties of molecular systems from unbiased Molecular Dynamics (MD). However, the implementation of reweighting schemes for MSMs to analyze biased simulations, for example produced by enhanced sampling techniques, is still at an early stage of development. Several dynamical reweighing approaches have been proposed, which can be classified as approaches based on (i) Kramers rate theory, (ii) rescaling of the probability density flux, (iii) reweighting by formulating a likelihood function, (iv) path reweighting. We present the state-of-the-art and discuss the methodological differences of these methods, their limitations and recent applications.

physics.chem-ph↗

arXiv2018

A complete hand-drawn sketch vectorization framework

Vectorizing hand-drawn sketches is a challenging task, which is of paramount importance for creating CAD vectorized versions for the fashion and creative workflows. This paper proposes a complete framework that automatically transforms noisy and complex hand-drawn sketches with different stroke types in a precise, reliable and highly-simplified vectorized model. The proposed framework includes a novel line extraction algorithm based on a multi-resolution application of Pearson's cross correlation and a new unbiased thinning algorithm that can get rid of scribbles and variable-width strokes to obtain clean 1-pixel lines. Other contributions include variants of pruning, merging and edge linking procedures to post-process the obtained paths. Finally, a modification of the original Schneider's vectorization algorithm is designed to obtain fewer control points in the resulting Bezier splines. All the proposed steps of the framework have been extensively tested and compared with state-of-the-art algorithms, showing (both qualitatively and quantitatively) its outperformance.

cs.CV↗

arXiv2017

Estimation of the infinitesimal generator by square-root approximation

For the analysis of molecular processes, the estimation of time-scales, i.e., transition rates, is very important. Estimating the transition rates between molecular conformations is -- from a mathematical point of view -- an invariant subspace projection problem. A certain infinitesimal generator acting on function space is projected to a low-dimensional rate matrix. This projection can be performed in two steps. First, the infinitesimal generator is discretized, then the invariant subspace is approxi-mated and used for the subspace projection. In our approach, the discretization will be based on a Voronoi tessellation of the conformational space. We will show that the discretized infinitesimal generator can simply be approximated by the geometric average of the Boltzmann weights of the Voronoi cells. Thus, there is a direct correla-tion between the potential energy surface of molecular structures and the transition rates of conformational changes. We present results for a 2d-diffusion process and Alanine dipeptide.

physics.comp-ph↗

arXiv2017

Girsanov reweighting for path ensembles and Markov state models

The sensitivity of molecular dynamics on changes in the potential energy function plays an important role in understanding the dynamics and function of complex molecules.We present a method to obtain path ensemble averages of a perturbed dynamics from a set of paths generated by a reference dynamics. It is based on the concept of path probability measure and the Girsanov theorem, a result from stochastic analysis to estimate a change of measure of a path ensemble. Since Markov state models (MSM) of the molecular dynamics can be formulated as a combined phase-space and path ensemble average, the method can be extended toreweight MSMs by combining it with a reweighting of the Boltzmann distribution. We demonstrate how to efficiently implement the Girsanov reweighting in a molecular dynamics simulation program by calculating parts of the reweighting factor "on the fly" during the simulation, and we benchmark the method on test systems ranging from a two-dimensional diffusion process to an artificial many-body system and alanine dipeptide and valine dipeptide in implicit and explicit water. The method can be used to study the sensitivity of molecular dynamics on external perturbations as well as to reweight trajectories generated by enhanced sampling schemes to the original dynamics.

cond-mat.stat-mech↗