The dynamical formulation of the optimal transport can be extended through various choices of the underlying geometry (kinetic energy), and … (see more)the regularization of density paths (potential energy). These combinations yield different variational problems (Lagrangians), encompassing many variations of the optimal transport problem such as the Schrödinger bridge, unbalanced optimal transport, and optimal transport with physical constraints, among others. In general, the optimal density path is unknown, and solving these variational problems can be computationally challenging. We propose a novel deep learning based framework approaching all of these problems from a unified perspective. Leveraging the dual formulation of the Lagrangians, our method does not require simulating or backpropagating through the trajectories of the learned dynamics, and does not need access to optimal couplings. We showcase the versatility of the proposed framework by outperforming previous approaches for the single-cell trajectory inference, where incorporating prior knowledge into the dynamics is crucial for correct predictions.

2024-07-07

Proceedings of the 41st International Conference on Machine Learning (published)

doi.org

proceedings.mlr.press

Efficient Evolutionary Search Over Chemical Space with Large Language Models

Haorui Wang

Marta Skreta

Cher Tian Ser

Wenhao Gao

Lingkai Kong

Felix Streith-Kalthoff

Chenru Duan

Yuchen Zhuang

Yue Yu

Yanqiao Zhu 0001

Yuanqi Du

Alán Aspuru-Guzik

Kirill Neklyudov

Chao Zhang

Molecular discovery, when formulated as an optimization problem, presents significant computational challenges because optimization objectiv… (see more)es can be non-differentiable. Evolutionary Algorithms (EAs), often used to optimize black-box objectives in molecular discovery, traverse chemical space by performing random mutations and crossovers, leading to a large number of expensive objective evaluations. In this work, we ameliorate this shortcoming by incorporating chemistry-aware Large Language Models (LLMs) into EAs. Namely, we redesign crossover and mutation operations in EAs using LLMs trained on large corpora of chemical information. We perform extensive empirical studies on both commercial and open-source models on multiple tasks involving property optimization, molecular rediscovery, and structure-based drug design, demonstrating that the joint usage of LLMs with EAs yields superior performance over all baseline models across single- and multi-objective settings. We demonstrate that our algorithm improves both the quality of the final solution and convergence speed, thereby reducing the number of required objective evaluations. Our code is available at http://github.com/zoom-wang112358/MOLLEO

2024-05-31

arXiv (published)

doi.org

arxiv.org

Doob's Lagrangian: A Sample-Efficient Variational Approach to Transition Path Sampling

Yuanqi Du

Michael Plainer

Rob Brekelmans

Chenru Duan

Frank Noé

Carla P. Gomes

Alán Aspuru-Guzik

Kirill Neklyudov

Rare event sampling in dynamical systems is a fundamental problem arising in the natural sciences, which poses significant computational cha… (see more)llenges due to an exponentially large space of trajectories. For settings where the dynamical system of interest follows a Brownian motion with known drift, the question of conditioning the process to reach a given endpoint or desired rare event is definitively answered by Doob's h-transform. However, the naive estimation of this transform is infeasible, as it requires simulating sufficiently many forward trajectories to estimate rare event probabilities. In this work, we propose a variational formulation of Doob's h-transform as an optimization problem over trajectories between a given initial point and the desired ending point. To solve this optimization, we propose a simulation-free training objective with a model parameterization that imposes the desired boundary conditions by design. Our approach significantly reduces the search space over trajectories and avoids expensive trajectory simulation and inefficient importance sampling estimators which are required in existing methods. We demonstrate the ability of our method to find feasible transition paths on real-world molecular simulation and protein folding tasks.

2023-12-31

arXiv (preprint)

doi.org

openreview.net

Structured Inverse-Free Natural Gradient Descent: Memory-Efficient & Numerically-Stable KFAC

Wu Lin

Felix Dangel

Runa Eschenhagen

Kirill Neklyudov

Agustinus Kristiadi

Richard E. Turner

Alireza Makhzani

Second-order methods such as KFAC can be useful for neural net training. However, they are often memory-inefficient since their precondition… (see more)ing Kronecker factors are dense, and numerically unstable in low precision as they require matrix inversion or decomposition. These limitations render such methods unpopular for modern mixed-precision training. We address them by (i) formulating an inverse-free KFAC update and (ii) imposing structures in the Kronecker factors, resulting in structured inverse-free natural gradient descent (SINGD). On modern neural networks, we show that SINGD is memory-efficient and numerically robust, in contrast to KFAC, and often outperforms AdamW even in half precision. Our work closes a gap between first- and second-order methods in modern low-precision training.

2023-12-31

ICML (published)

proceedings.mlr.press

TRAIL: Responsible AI for Professionals and Leaders

Mila Ventures Founder in Residence

AI Advantage: Productivity in Public Service

Kirill Neklyudov

Current Students

Publications

TRAIL: Responsible AI for Professionals and Leaders

Mila Ventures Founder in Residence

AI Advantage: Productivity in Public Service

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Kirill Neklyudov

Current Students

Publications