computational chemistry teams

Abstract: Guidance and composition of generative models have applications in visual design, chemistry, and biology. Logical guidance composes conditional scores exactly for diffusion models. However, Flow Matching (FM) and Stochastic Interpolants (SI) learn velocity fields. We show that negation and exclusive disjunction admit exact conditional velocity composition on any interpolant, whereas conjunction, and therefore any formula containing one, is exact on Gaussian paths but in general incurs a drift-interaction error, so composed velocities need not sample the logical target. LOGSI solves this by using score-based re-equilibration as our principled mechanism and falling back to the Gaussian-path velocity rule as an approximate transport predictor. In non-Gaussian bridge problems, generation alternates transport steps with score re-equilibration steps. On image trans fer (EMNIST to CMNIST, CelebA) and QM9 source-to-target molecular editing with logical attribute constraints, LOGSI improves rule conformity at the same network-evaluation budget over composed-velocity baselines, while also improving fidelity on the image tasks. More broadly, LOGSI applies wherever stochastic interpolants need guidance and logical combinations of constraints are natural.

Abstract: Latent diffusion models almost universally place a Gaussian prior on the VAE latent space. For base generation this default is unproblematic; under reinforcement-learning fine-tuning, however, it carries a structural limitation. The standard VAE's KL term does not merely ignore mode structure - it actively taxes separation and tightness. When data are multimodal, the ELBO optimum compresses distinct modes into an overlapping latent. RL fine-tuning amplifies this overlap: the score network is under-resolved on the saddle region between modes, dynamic-to-variational amplification rises sharply, and the collapse boundary beta_c is pushed far above its variational scale. On the real alanine-dipeptide Boltzmann distribution, a Gaussian-prior VAE collapses at beta_c = 0.224 while a mode-tracked Gaussian-mixture prior collapses at 0.00316, a 71x gap from the same pipeline. We trace this gap to a single geometric mediator, d_min/(2 sigma_0), and verify the causal chain through controlled interventions: moving geometry at fixed prior, and switching prior at matched geometry (full mediation; prior-label coefficient 0.995x, 95% CI [0.79, 1.25]). A three-source decomposition localises the amplification to the learned policy (zero ODE-solver contribution, bounded anchor mismatch); the coverage plateau is an unconditional benefit of mode-separating priors that no amount of RL capacity recovers. The remedy is conditional: a non-Gaussian prior is necessary precisely when the latent geometry would fall into overlap and the task is coverage-sensitive. A machine-checked theory skeleton supports the KL pricing structure - a divergent compactness tax under a Gaussian prior versus a finite assignment fee under a mixture - and the position-versus-plateau distinction delimits what is finite-resource from what requires changing the prior.

Abstract: Equivariant interatomic potentials enable accurate and efficient simulations of molecules and materials. Among them, models based on SO(2) convolutions reduce the cost of tensor products and achieve state-of-the-art accuracy, but their training remains time-consuming and memory-intensive. Existing training implementations materialize large edge tensors for representation transformations surrounding dense matrix multiplications, increasing memory usage and data movement. We observe that these transformations can be integrated into the model's existing dataflow, avoiding separate intermediate materialization. We introduce TrimSO(2), a fast and memory-efficient algorithm for SO(2)-based equivariant models. It realizes this principle through rotation on gather, recombination with activation, and inverse rotation on reduction, with support for the higher-order differentiation required for training. By avoiding intermediate materialization, TrimSO(2) delivers 2.71-16.73$\times$ operator speedups across forward, backward, and double backward and reduces model-level high-bandwidth memory traffic by 3.81-9.88$\times$. Finally, TrimSO(2) achieves 2.07-2.94$\times$ training speedups and 1.53-3.16$\times$ reductions in peak training memory over PyTorch implementations for official eSEN, UMA, and EquiformerV3 workloads on A100 and H100 GPUs.

Abstract: Energy-based models can represent distributions over discrete structures such as molecular graphs, but an energy that is accurate at equilibrium need not yield accurate samples when the sampler stops after a fixed number of steps. We introduce finite-horizon energy learning, which adapts the acceptance energy of a Metropolis--Hastings sampler to the distribution it returns after a prescribed number of steps, with initialization, proposals, and annealing schedule held fixed. For graph generation, a frozen pretrained model supplies initialization and proposals, and a learned energy governs acceptance. A training-only discriminator scores completed samples, and coupled continuations of the accepted and rejected branches of a proposal give an acceptance-gradient estimator that is unbiased for a fixed discriminator under stated conditions, without equilibrated negative samples or differentiation through discrete states. Generation uses the learned energy in the original single-trajectory sampler, without discriminator evaluations or reranking. On twelve pairwise binary targets with exactly evaluated terminal laws, learned energies have lower median terminal total variation than the equilibrium-correct energy in every tested short-horizon setting, and than its numerically tuned scalar multiple in most settings. On MOSES, a learned two-coefficient combination of pretrained Graph Energy Matching (GEM) potentials lowers FCD by 3.7--10.5\% relative to scale-calibrated GEM at matched sampling steps, with validity gains at the shortest budget and a sub-point validity trade-off at higher budgets.

Abstract: Molecular optical absorption spectroscopy provides a direct probe of electronic structure and is widely used for molecular identification, interpretation of photophysical behaviour, and planning of spectroscopy experiments. Calculating the absorption spectra using first-principle excited-state methods, however, is computationally demanding, at least compared to ground-state calculations, which limits their routine application across large molecular sets. Machine-learning (ML) surrogates can reduce this cost and allow rapid spectral prediction. However, their performance depends strongly on how molecular information is represented. Here, we compare using the ground-state electron density versus the molecular geometry as inputs to a ML model for predicting absorption spectra, for a training set of 6874 molecules selected from the QM7 dataset. For each of these molecules, the density was calculated using density functional theory (DFT) and the absorption spectrum was calculated using linear-response (LR) time-dependent DFT (TDDFT). Utilizing the ground-state density as the input to the ML model is motivated by the Hohenberg-Kohn and Runge-Gross theorems, and the fact that the ground-state density encodes information about bonding, charge localisation, and electronic delocalisation. Hence, it may be a more judicious starting point for the ML model compared to the geometry, as it effectively decouples the chemistry of the ground-state. The question we test is whether the benefits of using the density outweigh the (notprohibitive) penalty of requiring an additional single-point DFT calculation for the density. We find that the density-based convolutional neural network achieves a validation correlation of 0.9926, compared with 0.9795 for the best geometry-based graph model, reducing the residual decorrelation, by approximately 64%.

Abstract: Molecular systems have many degrees of freedom, but their metastable behavior can often be described by a few collective variables. Identifying these variables and estimating free energies along them from limited simulation data remains a challenging, important problem. Separate short trajectories may sample different metastable states without capturing transitions or establishing their relative equilibrium populations. For unbiased trajectories generated with the same Hamiltonian at a single temperature, alternate methods based on histogram reweighting cannot correct this imbalance. Here we present SPIBER, which combines the State Predictive Information Bottleneck (SPIB) with Generative Flow Networks (GFlowNets). SPIB uses deep learning to approximate slow degrees of freedom through a past-future information bottleneck, retaining information needed to predict future metastable states. We show that this compression limits conditional entropy variations in populated regions, allowing conditional mean potential energies, which are much easier to calculate, to be used to approximate free energy differences. Given sufficient local sampling to estimate these energies, they define the target distribution for GFlowNets, energy-based generative samplers that sample according to estimated thermodynamic stability rather than observed populations. For a particle in a radial double-well potential, for alanine dipeptide, and for the nine-residue peptide AIB9, SPIBER recovers free energy differences between sampled metastable states to within one thermal energy unit of reference values. The method combines collective-variable learning and free energy estimation in up to four latent dimensions, without requiring converged state populations or additional molecular dynamics simulations.

Abstract: AI co-scientists could accelerate computational research, but over a long-running study the workflow also has to stay inspectable, resumable and reproducible, which requires persistent computational state and provenance. Here we present OpenAI4S, an open-source scientific research agent built around the principle of \emph{Code as Action, Science as Sessions}. OpenAI4S combines a persistent computing runtime with research-session management: orchestration is handled through structured tool calls, while scientific actions are represented as complete code cells executed in persistent Python and R kernels. An append-only Action Ledger, per-cell execution records, versioned artifacts, environment records, and workspace checkpoints preserve how results were produced and support session recovery, branching, and extension. Configurable sandboxing, permission controls, and code and trajectory screening provide complementary safeguards. We evaluate OpenAI4S on 36 research scenarios spanning retrosynthesis, molecular dynamics, protein binder design, protein mutation, catalyst screening, and mineral spectroscopy, measuring scientific task accuracy, workflow completeness, and reproducibility of the resulting repositories. OpenAI4S achieves an overall score of 7.83, compared with 5.7--6.4 for a general-purpose coding harness evaluated with three frontier models, with the largest gains on long-horizon and computation-intensive workflows. These results suggest that integrating persistent execution with session-level provenance can improve the reliability of AI-assisted scientific workflows. Environment specification and full rerunnability remain weak for every evaluated system, ours included, so reproducibility is still an open problem for scientific agents. The system is available under the MIT license at \href{https://github.com/PKU-YuanGroup/OpenAI4S}{github.com/PKU-YuanGroup/OpenAI4S}.