arXiv subjects

Alex Zhavoronkov

Publications and source records attributed to Alex Zhavoronkov.

At least 19 recordsLinked to original sources

arXiv2026

MMAI Gym for Science: Training Liquid Foundation Models for Drug Discovery

General-purpose large language models (LLMs) that rely on in-context learning do not reliably deliver the scientific understanding and performance required for drug discovery tasks. Simply increasing model size or introducing reasoning tokens does not yield significant performance gains. To address this gap, we introduce the MMAI Gym for Science, a one-stop shop molecular data formats and modalities as well as task-specific reasoning, training, and benchmarking recipes designed to teach foundation models the 'language of molecules' in order to solve practical drug discovery problems. We use MMAI Gym to train an efficient Liquid Foundation Model (LFM) for these applications, demonstrating that smaller, purpose-trained foundation models can outperform substantially larger general-purpose or specialist models on molecular benchmarks. Across essential drug discovery tasks - including molecular optimization, ADMET property prediction, retrosynthesis, drug-target activity prediction, and functional group reasoning - the resulting model achieves near specialist-level performance and, in the majority of settings, surpasses larger models, while remaining more efficient and broadly applicable in the domain.

cs.LG↗

arXiv2026

Training Chemical Plausibility-Aware Large Language Models for Single-Step Retrosynthesis

Single-step retrosynthesis is a central component of computer-aided synthesis planning, yet its intrinsically one-to-many nature is poorly captured by single-answer evaluation and benchmarking protocols. To address this, we introduce Top-K prompting as a robust training and inference paradigm to better capture diverse, plausible reaction predictions. We compile CREED-CCV-2+USPTO-XL, an ultra-large-scale dataset of ~45.6 million verified reactions to train the C3LM (Chemistry Constraint-Consistent Language Model). By integrating fine-tuning with ChemCensor-based and novelty-oriented rewards, our model achieves state-of-the-art performance on the OOD URSA-expert-2026 benchmark. Further analysis of reaction uniqueness shows that LLMs and conventional models explore complementary reaction spaces, motivating ensemble-based retrosynthesis systems. Overall, our results establish Top-K, plausibility-aware training as a practical new direction for robust future LLM-based synthesis planning.

cs.LG↗

arXiv2026

Do Language Models Dream of Binding Molecules? Benchmarking LLMs under Spatial Constraints

Structure-based drug design (SBDD) leverages the 3D structure of protein targets, often complemented by other spatial constraints, to generate candidate binding molecules. While diffusion models have dominated as a leading paradigm for high-quality 3D molecule generation, LLM-based methods are rapidly emerging in molecular design and have shown competitive performance in pocket-conditioned molecular generation. However, their ability to reason about physics and 3D spatial environments is largely underexplored. In this work, we systematically analyze whether current general-purpose LLMs are capable of navigating complex 3D constraints compared to established baselines such as specialized diffusion models. We consider 3D ligand generation conditioned on protein pockets together with ligand- and interaction-derived spatial constraints, including anchor fragments, pharmacophore points, and mandatory pocket-ligand interactions. To enable this evaluation, we introduce 3D-Fit - a token-efficient benchmarking strategy for assessing LLM performance on multi-conditioned spatial molecule generation. Our findings reveal a clear pattern in LLM spatial capabilities: while they still lag behind state-of-the-art approaches, they are promising and can handle multiple spatial constraints simultaneously, enabling scaling to heterogeneous setups.

cs.LG↗

arXiv2026

Remembering George Smoot

George Smoot (1945-2025) was a major figure in observational cosmology, particularly through his role in the precision measurement of the CMB dipole and the discovery of the primordial CMB temperature anisotropy as part of the COBE team. This collection of 33 essays from collaborators, colleagues, students, and friends offers varied insights into the work, career, and life of George Smoot.

astro-ph.CO↗

arXiv2026

URSA: Chemistry-Aware Benchmark for Utilitarian Retrosynthesis Assessment

Synthesis planning aiming to find pathways of reactions for a target molecule is one of the most important and challenging tasks in drug discovery. Recent progress has produced both specialized deep-learning retrosynthesis systems and general-purpose large language models, but objective comparison remains difficult due to the lack of flexible, chemically interpretable benchmarking protocols. In the current study, we are introducing the URSA (Utilitarian RetroSynthesis Assessment) evaluation framework that provides the opportunity to benchmark the synthetic routes not only from a formal perspective, such as convergence to commercially available starting materials, but also from a chemical plausibility perspective, mimicking the way expert chemists evaluate the reactions and routes. The study covers a comprehensive evaluation of both conventional end-to-end retrosynthesis solutions and LLMs for the synthesis planning task on a set of novel, diverse target molecules with undisclosed synthetic routes, which represent realistic tasks in the daily drug design routine. We find that while LLMs can support high-level strategic planning, they currently underperform specialized retrosynthesis models in reliably solving synthesis planning tasks.

cs.LG↗

arXiv2026

Control Laws in Aging and Longevity: A Control Theory of Aging for Gerotherapeutic Drug Discovery

Existing aging theories describe what changes with age but do not prescribe how to intervene. We propose a control-theoretic framework that is not merely descriptive but prescriptive: it specifies which intervention, at which dose and sequence, under which safety constraints, will restore a measured biological state to a functional region. Aging is defined as progressive loss of safe controllability; biological age is the minimum safe control cost of functional restoration. Drugs are modeled as vector fields on biological state space whose non-commutativity, quantified by Lie brackets, predicts that intervention order determines outcome. The core differentiation from prior theories is operational: the framework outputs ranked targets, optimal sequences, safety-constrained protocols, and falsifiable predictions directly usable in drug discovery, rather than mechanistic ontologies or correlative biomarkers. We present a five-dimensional ODE model with analytic Lie-bracket derivation, a modality-aware control layer, three translational case studies, an implementation architecture with power analysis, and empirical scoring of aging interventions across five biological epochs. Twenty falsifiable predictions are enumerated. The central claim is that control-value reduction predicts translational success better than Hallmark annotation or biomarker reversal alone. If validated, this provides the missing interventional layer connecting aging biology to rational gerotherapeutic discovery.

q-bio.MN↗

arXiv2026

When Single Answer Is Not Enough: Rethinking Single-Step Retrosynthesis Benchmarks for LLMs

Recent progress has expanded the use of large language models (LLMs) in drug discovery, including synthesis planning. However, objective evaluation of retrosynthesis performance remains limited. Existing benchmarks and metrics typically rely on published synthetic procedures and Top-K accuracy based on single ground-truth, which does not capture the open-ended nature of real-world synthesis planning. We propose a new benchmarking framework for single-step retrosynthesis that evaluates both general-purpose and chemistry-specialized LLMs using ChemCensor, a novel metric for chemical plausibility. By emphasizing plausibility over exact match, this approach better aligns with human synthesis planning practices. We also introduce CREED, a novel dataset comprising millions of ChemCensor-validated reaction records for LLM training, and use it to train a model that improves over the LLM baselines under this benchmark.

cs.LG↗

arXiv2025

Peakspan: Defining, Quantifying and Extending the Boundaries of Peak Productive Lifespan

The unprecedented extension of the human lifespan necessitates a parallel evolution in how we quantify the quality of aging and its socioeconomic impact. Traditional metrics focusing on Healthspan (years free of disease) overlook the gradual erosion of physiological capacity that occurs even in the absence of illness, leading to declines in productivity and eventual lack of capacity to work. To address this critical gap, we introduce Peakspan: the age interval during which an individual maintains at least 90% of their peak functional performance in a specific physiological or cognitive domain. Our multi-system analysis reveals a profound misalignment: most biological systems reach maximal capacity in early adulthood, resulting in a Peakspan that is remarkably short relative to the total lifespan. This dissociation means humans now spend the majority of their adult lives in a "healthy but declined" state, characterized by a significant functional gap. We argue that extending Peakspan and developing strategies to restore function in post-peak individuals is the functional manifestation of rejuvenative biomedical progress and is essential for sustained economic growth in aging societies. Recognizing and tracking Peakspan, increasingly facilitated by artificial intelligence and foundational models of biological aging, is crucial for developing strategies to compress functional morbidity and maximize human potential across the life course.

q-bio.QM↗

arXiv2025

The Right to Be Remembered: Preserving Maximally Truthful Digital Memory in the Age of AI

Since the rapid expansion of large language models (LLMs), people have begun to rely on them for information retrieval. While traditional search engines display ranked lists of sources shaped by search engine optimization (SEO), advertising, and personalization, LLMs typically provide a synthesized response that feels singular and authoritative. While both approaches carry risks of bias and omission, LLMs may amplify the effect by collapsing multiple perspectives into one answer, reducing users ability or inclination to compare alternatives. This concentrates power over information in a few LLM vendors whose systems effectively shape what is remembered and what is overlooked. As a result, certain narratives, individuals or groups, may be disproportionately suppressed, while others are disproportionately elevated. Over time, this creates a new threat: the gradual erasure of those with limited digital presence, and the amplification of those already prominent, reshaping collective memory. To address these concerns, this paper presents a concept of the Right To Be Remembered (RTBR) which encompasses minimizing the risk of AI-driven information omission, embracing the right of fair treatment, while ensuring that the generated content would be maximally truthful.

cs.AI↗

arXiv2025

Engineering the Future of R&D: The Case for AI-Driven, Integrated Biotechnology Ecosystems

The escalating cost, extended timelines, and low success rates in pharmaceutical research demand a fundamental rethinking of biotechnology R&D infrastructure. This chapter introduces the concept of the AI-Integrated Biotechnology Hub, a purpose-built research ecosystem uniting residential, commercial, clinical, and research facilities under a central, AI-driven operating system. Designed as a multi-sided platform, the hub leverages continuous, multi-modal health data collection, advanced smart living environments, and federated learning models to enable secure, privacy-preserving biomedical research. By integrating real estate, biotechnology facilities, research hospitals, and community services, the model maximizes data utility, accelerates drug discovery, and enhances resident well-being. Transparency, accountability, and ethical stewardship are critical pillars of governance, enacted through dynamic consent, data trusts, and multi-stakeholder oversight. Scalable across urban and vertical architectures, this paradigm offers a viable, sustainable pathway toward improving healthspan, fostering innovation, and reshaping the economics of global drug development.

physics.soc-ph↗

arXiv2025

Enhancing Drug Discovery: Quantum Machine Learning for QSAR Prediction with Incomplete Data

Qualitative structure-activity relationship (QSAR) is important for drug discovery and offers valuable insights into the biological interactions of potential drug candidates. It has been demonstrated that QSAR can be accurately predicted by machine learning. However, data with poor quality and limited availability are always the most common and critical issues for medical-related applications for machine learning. In this manuscript, we aim to discuss the performance of classical and quantum classifiers in QSAR prediction and attempt to demonstrate the quantum advantages in the generalization power of the quantum classifier under conditions of limited data availability and a reduced number of features. By applying different data embedding methods followed by feature selection through principal component analysis (PCA), we find that the quantum classifier outperforms the classical one when a small number of features are selected and the number of training samples is limited. The generality of quantum advantages in other open datasets is also explored.

quant-ph↗

arXiv2024

BindGPT: A Scalable Framework for 3D Molecular Design via Language Modeling and Reinforcement Learning

Generating novel active molecules for a given protein is an extremely challenging task for generative models that requires an understanding of the complex physical interactions between the molecule and its environment. In this paper, we present a novel generative model, BindGPT which uses a conceptually simple but powerful approach to create 3D molecules within the protein's binding site. Our model produces molecular graphs and conformations jointly, eliminating the need for an extra graph reconstruction step. We pretrain BindGPT on a large-scale dataset and fine-tune it with reinforcement learning using scores from external simulation software. We demonstrate how a single pretrained language model can serve at the same time as a 3D molecular generative model, conformer generator conditioned on the molecular graph, and a pocket-conditioned 3D molecule generator. Notably, the model does not make any representational equivariance assumptions about the domain of generation. We show how such simple conceptual approach combined with pretraining and scaling can perform on par or better than the current best specialized diffusion models, language models, and graph neural networks while being two orders of magnitude cheaper to sample.

cs.LG↗

arXiv2024

nach0: Multimodal Natural and Chemical Languages Foundation Model

Large Language Models (LLMs) have substantially driven scientific progress in various domains, and many papers have demonstrated their ability to tackle complex problems with creative solutions. Our paper introduces a new foundation model, nach0, capable of solving various chemical and biological tasks: biomedical question answering, named entity recognition, molecular generation, molecular synthesis, attributes prediction, and others. nach0 is a multi-domain and multi-task encoder-decoder LLM pre-trained on unlabeled text from scientific literature, patents, and molecule strings to incorporate a range of chemical and linguistic knowledge. We employed instruction tuning, where specific task-related instructions are utilized to fine-tune nach0 for the final set of tasks. To train nach0 effectively, we leverage the NeMo framework, enabling efficient parallel optimization of both base and large model versions. Extensive experiments demonstrate that our model outperforms state-of-the-art baselines on single-domain and cross-domain tasks. Furthermore, it can generate high-quality outputs in molecular and textual formats, showcasing its effectiveness in multi-domain setups.

cs.CL↗

arXiv2024

Quantum Computing-Enhanced Algorithm Unveils Novel Inhibitors for KRAS

The discovery of small molecules with therapeutic potential is a long-standing challenge in chemistry and biology. Researchers have increasingly leveraged novel computational techniques to streamline the drug development process to increase hit rates and reduce the costs associated with bringing a drug to market. To this end, we introduce a quantum-classical generative model that seamlessly integrates the computational power of quantum algorithms trained on a 16-qubit IBM quantum computer with the established reliability of classical methods for designing small molecules. Our hybrid generative model was applied to designing new KRAS inhibitors, a crucial target in cancer therapy. We synthesized 15 promising molecules during our investigation and subjected them to experimental testing to assess their ability to engage with the target. Notably, among these candidates, two molecules, ISM061-018-2 and ISM061-22, each featuring unique scaffolds, stood out by demonstrating effective engagement with KRAS. ISM061-018-2 was identified as a broad-spectrum KRAS inhibitor, exhibiting a binding affinity to KRAS-G12D at $1.4 μM$. Concurrently, ISM061-22 exhibited specific mutant selectivity, displaying heightened activity against KRAS G12R and Q61H mutants. To our knowledge, this work shows for the first time the use of a quantum-generative model to yield experimentally confirmed biological hits, showcasing the practical potential of quantum-assisted drug discovery to produce viable therapeutics. Moreover, our findings reveal that the efficacy of distribution learning correlates with the number of qubits utilized, underlining the scalability potential of quantum computing resources. Overall, we anticipate our results to be a stepping stone towards developing more advanced quantum generative models in drug discovery.

quant-ph↗

arXiv2023

Exploring the Advantages of Quantum Generative Adversarial Networks in Generative Chemistry

De novo drug design with desired biological activities is crucial for developing novel therapeutics for patients. The drug development process is time and resource-consuming, and it has a low probability of success. Recent advances in machine learning and deep learning technology have reduced the time and cost of the discovery process and therefore, improved pharmaceutical research and development. In this paper, we explore the combination of two rapidly-developing fields with lead candidate discovery in the drug development process. First, Artificial intelligence has already been demonstrated to successfully accelerate conventional drug design approaches. Second, quantum computing has demonstrated promising potential in different applications, such as quantum chemistry, combinatorial optimizations, and machine learning. This manuscript explores hybrid quantum-classical generative adversarial networks (GAN) for small molecule discovery. We substituted each element of GAN with a variational quantum circuit (VQC) and demonstrated the quantum advantages in the small drug discovery. Utilizing a VQC in the noise generator of a GAN to generate small molecules achieves better physicochemical properties and performance in the goal-directed benchmark than the classical counterpart. Moreover, we demonstrate the potential of a VQC with only tens of learnable parameters in the generator of GAN to generate small molecules. We also demonstrate the quantum advantage of a VQC in the discriminator of GAN. In this hybrid model, the number of learnable parameters is significantly less than the classical ones, and it can still generate valid molecules. The hybrid model with only tens of training parameters in the quantum discriminator outperforms the MLP-based one in terms of both generated molecule properties and the achieved KL divergence.

quant-ph↗

arXiv2022

AlphaFold Accelerates Artificial Intelligence Powered Drug Discovery: Efficient Discovery of a Novel Cyclin-dependent Kinase 20 (CDK20) Small Molecule Inhibitor

The AlphaFold computer program predicted protein structures for the whole human genome, which has been considered as a remarkable breakthrough both in artificial intelligence (AI) application and structural biology. Despite the varying confidence level, these predicted structures still could significantly contribute to structure-based drug design of novel targets, especially the ones with no or limited structural information. In this work, we successfully applied AlphaFold in our end-to-end AI-powered drug discovery engines constituted of a biocomputational platform PandaOmics and a generative chemistry platform Chemistry42, to identify a first-in-class hit molecule of a novel target without an experimental structure starting from target selection towards hit identification in a cost- and time-efficient manner. PandaOmics provided the targets of interest and Chemistry42 generated the molecules based on the AlphaFold predicted structure, and the selected molecules were synthesized and tested in biological assays. Through this approach, we identified a small molecule hit compound for CDK20 with a Kd value of 8.9 +/- 1.6 uM (n = 4) within 30 days from target selection and after only synthesizing 7 compounds. Based on the available data, the second round of AI-powered compound generation was conducted and through which, a more potent hit molecule, ISM042-2 048, was discovered with a Kd value of 210.0 +/- 42.4 nM (n = 2), within 30 days and after synthesizing 6 compounds from the discovery of the first hit ISM042-2-001. To the best of our knowledge, this is the first reported small molecule targeting CDK20 and more importantly, this work is the first demonstration of AlphaFold application in the hit identification process in early drug discovery.

q-bio.BM↗

arXiv2021

Chemistry42: An AI-based platform for de novo molecular design

Chemistry42 is a software platform for de novo small molecule design that integrates Artificial Intelligence (AI) techniques with computational and medicinal chemistry methods. Chemistry42 is unique in its ability to generate novel molecular structures with predefined properties validated through in vitro and in vivo studies. Chemistry42 is a core component of Insilico Medicine Pharma.ai drug discovery suite that also includes target discovery and multi-omics data analysis (PandaOmics) and clinical trial outcomes predictions (InClinico).

cs.AI↗

arXiv2020

Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models

Generative models are becoming a tool of choice for exploring the molecular space. These models learn on a large training dataset and produce novel molecular structures with similar properties. Generated structures can be utilized for virtual screening or training semi-supervised predictive models in the downstream tasks. While there are plenty of generative models, it is unclear how to compare and rank them. In this work, we introduce a benchmarking platform called Molecular Sets (MOSES) to standardize training and comparison of molecular generative models. MOSES provides a training and testing datasets, and a set of metrics to evaluate the quality and diversity of generated structures. We have implemented and compared several molecular generation models and suggest to use our results as reference points for further advancements in generative chemistry research. The platform and source code are available at https://github.com/molecularsets/moses.

cs.LG↗