Papers for
drug design teams
Papers whose findings have a practical use for this group, as judged from the abstract. Open a paper to read what it means in practice.
RNA molecular dynamics dataset captures diverse conformations
mdRNAcat: A Molecular Dynamics RNA Catalog of REST2 Conformational Ensembles
Abstract: Learning molecular models of RNA requires simulation data that capture conformational variability and provide consistent physical training signals. Here, we introduce mdRNAcat, a curated dataset of all-atom molecular dynamics (MD) simulations of 48 RNA systems selected to promote sequence diversity. Each system is simulated using replica-exchange with solute scaling (REST2), with 32 Hamiltonian states and production lengths of 200-300 ns per state. The dataset provides atomic coordinates, instantaneous forces, and forces reevaluated under the unscaled reference Hamiltonian, together with structural annotations and replica-exchange metadata. Coordinates and forces are available at 1 ps intervals for the reference state and 100 ps intervals across all states in a standardized HDF5 format. We characterize conformational sampling, exchange behavior, base pairing, and sugar-pucker distributions to document the properties of the simulated ensembles. mdRNAcat provides a reusable resource for developing and evaluating data-driven RNA models, including coarse-grained force fields.
Ml speeds up calculating atomic energy changes in large molecules
Colour me shocked: Exact Molecular Hessians from local MLIPs in O(N) time using sparse differentiation!
Abstract: The Hessian of the energy with respect to the nuclear positions is indispensable in atomistic modelling. However, constructing this matrix requires $O(N)$ Hessian vector products, traditionally limiting high-accuracy Hessians to small systems. Machine learning interatomic potentials (MLIPs) have accelerated atomistic modelling by providing highly accurate energies and forces at $O(N)$ cost, yet the resulting $O(N^2)$ cost of Hessians remains a practical bottleneck for large systems. Based on the insight that we can derive the sparsity pattern for an MLIP's Hessians in closed form, we show in this paper how to use techniques from sparse automatic differentiation to reduce the cost of a local MLIP's Hessians to a system-size-independent number of Hessian-vector products, yielding overall $O(N)$ total cost without any approximations. We benchmark our approach on a variety of systems ranging from alkane chains to water clusters to $A\beta40$ conformers. Depending on the MLIP configuration, we achieve the linear scaling regime already on relatively small systems, resulting in large runtime reductions between 2$\times$-15$\times$ for these systems. This opens up the possibility of scaling high-accuracy MLIP Hessians to very large systems, such as proteins that were previously inaccessible.