Giri P. Krishnan

Tyler L. Hayes, Giri P. Krishnan

Models such as AlphaFold2 and OpenFold have transformed protein structure prediction, yet their inner workings remain poorly understood. We present a methodology to systematically evaluate the contribution of individual OpenFold components to structure prediction accuracy. We identify several components that are critical for most proteins, while others vary in importance across proteins. We further show that the contribution of several components is correlated with protein length. These findings provide insight into how OpenFold achieves accurate predictions and highlight directions for interpreting protein prediction networks more broadly.

Anthony Bazhenov, Pahan Dewasurendra, Giri P. Krishnan et al.

Artificial neural networks (ANNs) show limited performance with scarce or imbalanced training data and face challenges with continuous learning, such as forgetting previously learned data after new tasks training. In contrast, the human brain can learn continuously and from just a few examples. This research explores the impact of 'sleep', an unsupervised phase incorporating stochastic activation with local Hebbian learning rules, on ANNs trained incrementally with limited and imbalanced datasets, specifically MNIST and Fashion MNIST. We discovered that introducing a sleep phase significantly enhanced accuracy in models trained with limited data. When a few tasks were trained sequentially, sleep replay not only rescued previously learned information that had been catastrophically forgetting following new task training but often enhanced performance in prior tasks, especially those trained with limited data. This study highlights the multifaceted role of sleep replay in augmenting learning efficiency and facilitating continual learning in ANNs.

Jean Erik Delanois, Aditya Ahuja, Giri P. Krishnan et al.

Artificial neural networks are often overconfident, undermining trust because their predicted probabilities do not match actual accuracy. Inspired by biological sleep and the role of spontaneous replay in memory and learning, we introduce Sleep Replay Consolidation (SRC), a novel calibration approach. SRC is a post-training, sleep-like phase that selectively replays internal representations to update network weights and improve calibration without supervised retraining. Across multiple experiments, SRC is competitive with and complementary to standard approaches such as temperature scaling. Combining SRC with temperature scaling achieves the best Brier score and entropy trade-offs for AlexNet and VGG19. These results show that SRC provides a fundamentally novel approach to improving neural network calibration. SRC-based calibration offers a practical path toward more trustworthy confidence estimates and narrows the gap between human-like uncertainty handling and modern deep networks.

Austin M. Wallace, C. David Sherrill, Giri P. Krishnan

Ab initio quantum chemical methods for accurately computing interactions between molecules have a wide range of applications but are often computationally expensive. Hence, selecting an appropriate method based on accuracy and computational cost remains a significant challenge due to varying performance of methods. In this work, we propose a framework based on an ensemble of $Δ$-ML models trained on features extracted from a pre-trained atom-pairwise neural network to predict the error of each method relative to all other methods including the ``gold standard'' coupled cluster with single, double, and perturbative triple excitations at the estimated complete basis set limit [CCSD(T)/CBS]. Our proposed approach provides error estimates across various levels of theories and identifies the computationally efficient approach for a given error range utilizing only a subset of the dataset. Further, this approach allows comparison between various theories. We demonstrate the effectiveness of our approach using an extended BioFragment dataset, which includes the interaction energies for common biomolecular fragments and small organic dimers. Our results show that the proposed framework achieves very small mean-absolute-errors below 0.1 kcal/mol regardless of the given method. Furthermore, by analyzing all-to-all $Δ$-ML models for present levels of theory, we identify method groupings that align with theoretical hypotheses, providing evidence that $Δ$-ML models can easily learn corrections from any level of theory to any other level of theory.

Tyler L. Hayes, Giri P. Krishnan, Maxim Bazhenov et al.

Replay is the reactivation of one or more neural patterns, which are similar to the activation patterns experienced during past waking experiences. Replay was first observed in biological neural networks during sleep, and it is now thought to play a critical role in memory formation, retrieval, and consolidation. Replay-like mechanisms have been incorporated into deep artificial neural networks that learn over time to avoid catastrophic forgetting of previous knowledge. Replay algorithms have been successfully used in a wide range of deep learning methods within supervised, unsupervised, and reinforcement learning paradigms. In this paper, we provide the first comprehensive comparison between replay in the mammalian brain and replay in artificial neural networks. We identify multiple aspects of biological replay that are missing in deep learning systems and hypothesize how they could be utilized to improve artificial neural networks.