Molecular conformation optimization is crucial to computer-aided drug discovery and materials design. Traditional energy minimization techniques rely on iterative optimization methods that use molecular forces calculated by a physical simulator (oracle) as anti-gradients. However, this is a computationally expensive approach that requires many interactions with a physical simulator. One way to accelerate this procedure is to replace the physical simulator with a neural network. Despite recent progress in neural networks for molecular conformation energy prediction, such models are prone to errors due to distribution shift, leading to inaccurate energy minimization. We find that the quality of energy minimization with neural networks can be improved by providing optimization trajectories as additional training data. Still, obtaining complete optimization trajectories demands a lot of additional computations. To reduce the required additional data, we present the Gradual Optimization Learning Framework (GOLF) for energy minimization with neural networks. The framework consists of an efficient data-collecting scheme and an external optimizer. The external optimizer utilizes gradients from the energy prediction model to generate optimization trajectories, and the data-collecting scheme selects additional training data to be processed by the physical simulator. Our results demonstrate that the neural network trained with GOLF performs \textit{on par} with the oracle on a benchmark of diverse drug-like molecules using significantly less additional data.

Methods of computational quantum chemistry provide accurate approximations of molecular properties crucial for computer-aided drug discovery and other areas of chemical science. However, high computational complexity limits the scalability of their applications.Neural network potentials (NNPs) are a promising alternative to quantum chemistry methods, but they require large and diverse datasets for training.This work presents a new dataset and benchmark called $\nabla^2$DFT that is based on the nablaDFT.It contains twice as much molecular structures, three times more conformations, new data types and tasks, and state-of-the-art models.The dataset includes energies, forces, 17 molecular properties, Hamiltonian and overlap matrices, and a wavefunction object.All calculations were performed at the DFT level ($\omega$B97X-D/def2-SVP) for each conformation. Moreover, $\nabla^2$DFT is the first dataset that contains relaxation trajectories for a substantial number of drug-like molecules. We also introduce a novel benchmark for evaluating NNPs in molecular property prediction, Hamiltonian prediction, and conformational optimization tasks. Finally, we propose an extendable framework for training NNPs and implement 10 models within it.