The Comprehensive VS Platform with AI Engine (CVSP-AIE) for drug discovery from compound libraries integrates three AI models: KarmaDock, a fast docking model that directly updates atomic coordinates; CarsiDock, an accurate docking model that predicts protein-ligand distances and reconstructs binding poses; and RTMScore, an accurate scoring model that learns residue-atom distance distributions for affinity prediction.
Current structure-based drug design generative models often struggle to faithfully recapitulate genuine ligand-protein binding interactions. Instead, under the coupling of implicit learning architectures and biased training data, they tend to learn spurious statistical correlations. To address this, we propose EIP-Diff (Explicit Interaction-Prompted Diffusion), an architecture featuring a novel explicit interaction-prompt embedding mechanism that is better suited for real-world target-specific drug design. This architecture replaces biased implicit learning with explicit, residue-level biological guidance, thereby promoting more fine-grained geometric fidelity and more precise interaction-aware conditioning. To fully realize the capabilities of EIP-Diff and provide a reliable basis for performance evaluation, we further constructed CrystalData set, which provides higher-fidelity and less-biased structural supervision than existing data sets. This explicit architecture markedly improves distribution consistency: even when trained on the crossdocked data set, EIP-Diff achieves the highest alignment with authentic pharmacological distributions among evaluated models. Training on CrystalData set further enhances this alignment and improves 3D geometric accuracy, while retaining strong controllability, high chemical space coverage, and near-perfect uniqueness. In addition, target-based validation on KAT6A and YTHDC1 confirmed that EIP-Diff accurately recapitulates native-like binding modes. Furthermore, in a real-world drug design task against IDO1, we successfully designed a novel lead compound with nanomolar potency (IC50 = 0.31 nM). These results demonstrate that the EIP-Diff architecture can explicitly leverage experimentally derived structural data and biologically meaningful interaction information for target-specific molecular generation, thereby enabling its effective application to real-world structure-based drug design.
Huabin Du, Mingyang Wang, M. Luo et al.· Journal of the American Chem...· 0 citations
The null token is turned into a diagnostic lens on hallucination and motivate evaluating abstention methods by both suppression and deletion costs, rather than by hallucination reduction alone.
Kirill Borodin, V. Kudryavtsev, Ivan Viakhirev et al.· 0 citations
Scaling transformer language models creates an inherent tension between expressivity and memory efficiency. While unique weights across layers preserve functional specialization---from input-grounding to abstract refinement---they incur a substantial memory footprint. Conversely, standard depth-sharing enforces uniform transformations that collapse representational diversity and degrade modeling quality. We introduce Gated Recurrent Transformer, a recurrent depth transformer where fixed-depth prelude and coda blocks bracket a single shared core iterated R times. Inspired by gated recurrent neural networks, we employ a lightweight projection and an elementwise update gate---conditioned on the hidden state, the fixed prelude output, and noise resampled at every step---to modulate the recurrent update. This allows the model to specialize the input to the same few layers across recurrences, rather than requiring many unique layers to achieve functional diversity. Under an isoFLOPS constraint, a 3-layer Gated Recurrent Transformer matches the accuracy of a 12-layer GPT-2 Small baseline with similar training and inference FLOPs, and leads MoR and heavy-tail depth sampling in all nine scale-by-budget cells; at medium and large scale it approaches dense quality at the standard token budget and overtakes it at medium scale once that budget is doubled. Under an isoPARAMS constraint, deeper recurrence achieves a 2.76 validation loss versus 2.84 for a non-recurrent counterpart at matched parameter and data budget. Our results demonstrate that adaptive depth reuse is a principled strategy for trading parameters for quality: at large scale, 63% fewer parameters and 59% less peak decoding memory for a 10% increase in compiled generation latency.
Amr Hegazy, Amr Alanwar, Mostafa Elhoushi· 0 citations
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Belayer handles failures in both rollout engines and environment execution while targeting low failure-free overhead, and shows low measured overhead during failure-free training, a worker-recovery-time reduction of up to 42 times faster compared with a full engine cold start, and 1.5 to 3.5 times faster recovery from environment failures.
Jiecheng Zhou, Qi Hu, Peng Sun et al.· 0 citations
This work proposes a class of Multi-Objective Moreau Envelope based Hessian-free Algorithms (MOMEHA) to solve the multi-objective bilevel learning problems with nonconvex lower level and proposes a momentum-based variant of MOMEHA (i.e., MB-MOMEHA) method to solve the stochastic multi-objective bilevel learning problems.
This work substantially expand the IMPROVE benchmark through large-scale integration of pharmacogenomic data, primarily from PharmacoDB, together with additional smaller data sources, which includes millions of drug response measurements, broader multi-omics coverage, and a major increase in chemical diversity, adding more than 50,000 compounds.
Vincent Lavelle, Yitan Zhu, Kaitlyn Marlor et al.· 0 citations
For mirror descent generated by a Legendre kernel, perhaps one of the most basic question in optimization is this: must every accumulation point of a bounded mirror descent sequence be Karush--Kuhn--Tucker (KKT) stationary under proper stepsizes? We show that the answer is no. A longstanding obstacle to resolving this question is the boundary blow-up of the Legendre gradient: it keeps every mirror step in the interior, while at a boundary limit, the inverse entropy metric vanishes on active coordinates and can erase the dual-feasibility in the KKT system. We construct $C^\infty$ objectives and bounded sequences generated by the Shannon-entropic mirror descent on the nonnegative orthant $\R_+^n$, for every $n\geq 3$, and on the probability simplex $\Delta_n$, for every $n\geq 4$, such that, in each case, the set of accumulation points is a smooth boundary circle containing a nonempty relatively open arc of non-KKT points. The steps satisfy $\alpha_k\asymp k^{-\beta}$ with $\beta\in(1/2,1)$, the objective values are nonincreasing, and the objectives are entropy-relatively smooth. Hence the pathology stems from the degeneracy of the Bregman geometry at the boundary, rather than from failure of descent, or improper stepsizes. To the best of our knowledge, these provide the first counterexamples to KKT accumulation for bounded mirror descent sequences with nonincreasing objective values.
Post-training alignment is often shallow, eroding under fine-tuning. It remains untested as to whether constitutional midtraining interventions can produce durable alignment when cleanly isolated from post-training. We build a 394M-token constitutional corpus from Anthropic's Constitution and apply constitutional midtraining at 120B scale, where principled, values-based content is inserted into midtraining. A 2x2 design (curriculum ordering x deliberative reasoning) was used to produce four constitutionally midtrained conditions, plus a control, which were evaluated on self-generated and established benchmarks including alignment under pressure, value conflict resolution, blackmail, and emergent misalignment. All models were evaluated across three stages: post-midtraining, post-SFT, and post-benign fine-tuning. Constitutionally midtrained models outperformed the control on alignment generalization and durability, notably on blackmail: SFT instilled a blackmail propensity in all models, but constitutional midtraining blunted it, with the advantage surviving benign fine-tuning (-17.5pp). This durability did not extend to settings that required active resistance to in-context pressure or conflict, where the advantage attenuates after SFT. The presence of constitutional content at midtraining also mattered more than its structure, and constitutional midtraining incurred no capability cost, on average, at any stage (MMLU, ARC-Easy, piqa, GSM8K). A modest amount of constitutional content at midtraining could therefore yield broad, persistent alignment gains, offering a cheap, complementary addition to SFT-centered pipelines. Code, data, and models are available.
Desiree Cho, Cameron Tice, Bernie Hogan et al.· 0 citations
The goal of this study is to understand practitioners'decision making process and security considerations in selecting and integrating AI components through an exploratory semi-structured interview study, and distill the findings into actionable recommendations for AI adopters, model providers, and researchers.
Mahzabin Tamanna, Elizabeth Lin, Sparsha Gowda et al.· 0 citations
This work investigates MRI-based Microbial Density Stratification as a patient-level representation learning task, and Center Heatmap-driven Macro-micro modeling Network (CHM-Net) is introduced for this task, establishing the link between imaging phenotypes and microbial states through center heatmap-guided small-lesion response localization.
Jiaming Liang, Hao Chen, Ting Li et al.· 0 citations
Reinforcement learning (RL) post-training for large language models (LLMs) follows a efficient paradigm of "rollout then update", which inevitably results in off-policy training data. To resolve this, Importance sampling (IS) is proposed, while the token-level ratios compound over long sequences, causing severe variance exploded. A natural idea is "transferring" these off-policy token into on-policy token, so that the importance scores for correction are unnecessary. Following this idea, we propose Selective Importance Sampling (SIS), which is inspired by rejection sampling. Concretely, SIS implements by viewing off-policy model as proposal distribution, and implement a token-level rejection test: accepted tokens are viewed as on-policy, so that receive unit importance score, while rejected tokens retain the standard IS correction. Our proposed SIS is theoretically proved reducing the gap between token-level and sequence-level off-policy gradient estimators. The SIS acts as a plug-in that only modifies the importance ratio in the policy loss, adding negligible wall-clock overhead, and can be combine with a vast vary of RL post-training algorithms. Experiments on dense and MoE LLMs across math and agent benchmarks show that SIS consistently improves all objectives, while providing substantially stronger robustness under off-policy data.
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
MIT News · Artificial Intelligence· news.mit.eduAug 24, 2026
A new method for surgically removing training examples from a model reveals that as datasets grow, the link between what a model learns and what it produces dissolves.
