arXiv subjects

James Vuckovic

Publications and source records attributed to James Vuckovic.

8 recordsLinked to original sources

arXiv2026

Latent-Y: A Lab-Validated Autonomous Agent for De Novo Drug Design

Drug discovery relies on iterative expert workflows that are slow to parallelize and difficult to scale. Here we introduce Latent-Y, an AI agent that autonomously executes complete antibody design campaigns from text prompts, covering literature review, target analysis, epitope identification, candidate design, computational validation, and selection of lab-ready sequences. Latent-Y is integrated into the Latent Labs Platform, where it operates in the same environment as drug-discovery experts with access to bioinformatics tools, biological databases, and scientific literature. The agent can run fully autonomously end-to-end, or collaboratively, where researchers review progress, provide feedback, and direct subsequent steps. Candidate antibodies are generated using Latent-X2, our frontier generative model for drug-like antibody design. We demonstrate the agent's capability across three distinct campaign types: epitope discovery guided by therapeutic specifications, cross-species binder design, and autonomous design from a scientific publication targeting human transferrin receptor for blood-brain barrier crossing. Across nine targets, Latent-Y produced lab-confirmed nanobody binders against six, achieving a 67% target-level success rate with binding affinities reaching the single-digit nanomolar range, without human filtering or intervention. In user studies, experts working with Latent-Y completed design campaigns 56 times faster than independent expert time estimates, compressing weeks of work into hours. Because Latent-X2 is a general-purpose atomic-level model for biologics design, the same agent architecture naturally extends to macrocyclic peptide and mini-binder design campaigns, broadening autonomous discovery across therapeutic modalities. Latent-Y is available to selected partners at https://platform.latentlabs.com.

q-bio.BM↗

arXiv2026

Propagation of Chaos for Nonlinear Markov Chains

We study 1-Wasserstein propagation of chaos for "McKean-type" nonlinear Markov chains and their associated interacting particle systems. This paper is organized into two parts: the first part combines arguments from various areas of nonlinear Markov theory into a systematic treatment of quantitative, nonasymptotic empirical measure estimates and propagation of chaos, with Lipschitz regularity as the primary tool. We also study extensions to uniform-in-time propagation of chaos and improved convergence rates under stronger assumptions such as transportation inequalities, modified metrics, or geometric ergodicity. The second part of this work consists of two detailed applications of our results to specific systems of interest: an Euler-Maruyama scheme for the standard McKean-Vlasov diffusion, and particle filtering via Feynman-Kac distribution flows.

math.PR↗

arXiv2025

Drug-like antibodies with low immunogenicity in human panels designed with Latent-X2

Drug discovery has long sought computational systems capable of designing drug-like molecules directly: developable and non-immunogenic from the start. Here we introduce Latent-X2, a frontier generative model that achieves this goal through zero-shot design of antibodies with strong binding affinities, drug-like properties, and, for the first time for any de novo generated antibody, confirmed low immunogenicity in human donor panels. Latent-X2 is an all-atom model conditioned on target structure, epitope specification, and optional antibody framework, jointly generating sequences and structures while modelling the bound complex. Testing only 4 to 24 designs per target in each modality, we successfully generated VHH and scFv antibodies against 9 of 18 evaluated targets, achieving a 50% target-level success rate with picomolar to nanomolar binding affinities. Designed molecules exhibit developability profiles that match or exceed those of approved antibody therapeutics, including expression yield, aggregation propensity, polyreactivity, hydrophobicity, and thermal stability, without optimization, filtering, or selection. In the first immunogenicity assessment of any AI-generated antibody, representative de novo VHH binders targeting TNFL9 exhibit both potent target engagement and low immunogenicity across T-cell proliferation and cytokine release assays. The model generalizes beyond antibodies: against K-Ras, long considered undruggable, we generated macrocyclic peptide binders competitive with trillion-scale mRNA display screens. These properties emerge directly from the model, demonstrating the therapeutic viability of zero-shot molecular design, now available without AI infrastructure or coding expertise at https://platform.latentlabs.com.

q-bio.BM↗

arXiv2024

Sequence-Augmented SE(3)-Flow Matching For Conditional Protein Backbone Generation

Proteins are essential for almost all biological processes and derive their diverse functions from complex 3D structures, which are in turn determined by their amino acid sequences. In this paper, we exploit the rich biological inductive bias of amino acid sequences and introduce FoldFlow-2, a novel sequence-conditioned SE(3)-equivariant flow matching model for protein structure generation. FoldFlow-2 presents substantial new architectural features over the previous FoldFlow family of models including a protein large language model to encode sequence, a new multi-modal fusion trunk that combines structure and sequence representations, and a geometric transformer based decoder. To increase diversity and novelty of generated samples -- crucial for de-novo drug design -- we train FoldFlow-2 at scale on a new dataset that is an order of magnitude larger than PDB datasets of prior works, containing both known proteins in PDB and high-quality synthetic structures achieved through filtering. We further demonstrate the ability to align FoldFlow-2 to arbitrary rewards, e.g. increasing secondary structures diversity, by introducing a Reinforced Finetuning (ReFT) objective. We empirically observe that FoldFlow-2 outperforms previous state-of-the-art protein structure-based generative models, improving over RFDiffusion in terms of unconditional generation across all metrics including designability, diversity, and novelty across all protein lengths, as well as exhibiting generalization on the task of equilibrium conformation sampling. Finally, we demonstrate that a fine-tuned FoldFlow-2 makes progress on challenging conditional design tasks such as designing scaffolds for the VHH nanobody.

cs.LG↗

arXiv2022

Nonlinear MCMC for Bayesian Machine Learning

We explore the application of a nonlinear MCMC technique first introduced in [1] to problems in Bayesian machine learning. We provide a convergence guarantee in total variation that uses novel results for long-time convergence and large-particle ("propagation of chaos") convergence. We apply this nonlinear MCMC technique to sampling problems including a Bayesian neural network on CIFAR10.

stat.ML↗

arXiv2021

On the Regularity of Attention

Attention is a powerful component of modern neural networks across a wide variety of domains. In this paper, we seek to quantify the regularity (i.e. the amount of smoothness) of the attention operation. To accomplish this goal, we propose a new mathematical framework that uses measure theory and integral operators to model attention. We show that this framework is consistent with the usual definition, and that it captures the essential properties of attention. Then we use this framework to prove that, on compact domains, the attention operation is Lipschitz continuous and provide an estimate of its Lipschitz constant. Additionally, by focusing on a specific type of attention, we extend these Lipschitz continuity results to non-compact domains. We also discuss the effects regularity can have on NLP models, and applications to invertible and infinitely-deep networks.

stat.ML↗

arXiv2020

A Mathematical Theory of Attention

Attention is a powerful component of modern neural networks across a wide variety of domains. However, despite its ubiquity in machine learning, there is a gap in our understanding of attention from a theoretical point of view. We propose a framework to fill this gap by building a mathematically equivalent model of attention using measure theory. With this model, we are able to interpret self-attention as a system of self-interacting particles, we shed light on self-attention from a maximum entropy perspective, and we show that attention is actually Lipschitz-continuous (with an appropriate metric) under suitable assumptions. We then apply these insights to the problem of mis-specified input data; infinitely-deep, weight-sharing self-attention networks; and more general Lipschitz estimates for a specific type of attention studied in concurrent work.

stat.ML↗

arXiv2018

Kalman Gradient Descent: Adaptive Variance Reduction in Stochastic Optimization

We introduce Kalman Gradient Descent, a stochastic optimization algorithm that uses Kalman filtering to adaptively reduce gradient variance in stochastic gradient descent by filtering the gradient estimates. We present both a theoretical analysis of convergence in a non-convex setting and experimental results which demonstrate improved performance on a variety of machine learning areas including neural networks and black box variational inference. We also present a distributed version of our algorithm that enables large-dimensional optimization, and we extend our algorithm to SGD with momentum and RMSProp.

stat.ML↗