ProGen models protein sequences for synthetic biology.
problem Generating proteins without structural annotations.
method Trained a 1.2B-parameter language model on 280M protein sequences.
result ProGen generates proteins with fine-grained control and accuracy.
Study improves LLMs for PPI analysis by addressing uncertainty.
problem Uncertainty in LLM predictions for PPIs.
method Fine-tuned LLaMA-3 and BioMedGPT models, LoRA ensembles, Bayesian LoRA for UQ.
result Competitive PPI identification performance across diverse disease contexts.
A new approach to protein language models combines latent space prediction with masked language modeling.
problem Improving protein language models by predicting amino acid identities at masked positions.
method A variant of masked language modeling that predicts latent targets only at masked positions, retaining the MLM cross-entropy.
result The new approach outperforms pure masked language modeling on 11 out of 16 downstream tasks.
ProtTrans models predict protein features without evolutionary info.
problem Predicting protein features from amino acid sequences.
method Self-supervised deep learning on large protein datasets.
result ProtT5 embeddings outperform state-of-the-art for per-residue predictions.
Bridging the exponentially growing gap between the numbers of unlabeled and labeled protein sequences, several studies adopted semi-supervised learning for protein sequence modeling. In these studies, models were pre-trained with a substantial amount of unlabeled data, and the representations were transferred to variou…
New model uses pretrained biochemical language models to generate drug compounds.
problem Developing novel compounds targeting specific proteins.
method Exploits pretrained language models to initialize and fine-tune targeted molecule generation models.
result Warm-started models outperform baseline models, with one-stage strategy showing better generalization.
Identification of high affinity drug-target interactions is a major research question in drug discovery. Proteins are generally represented by their structures or sequences. However, structures are available only for a small subset of biomolecules and sequence similarity is not always correlated with functional similar…
NLP techniques improve drug discovery by analyzing chemical and protein text.
problem Improving drug discovery through better analysis of chemical and protein text.
method Natural language processing techniques applied to biochemical entities.
result Enhanced prediction of molecular properties and design of novel molecules.
Generative models often misrepresent class frequencies; this paper calibrates them.
problem Miscalibration of class frequencies in generative models.
method Formulated as constrained optimization, using surrogate objectives to approximate constraints.
result Significant reduction in calibration error across various models and applications.
Paper improves Tm prediction of protein fragments using sparsity and probabilistic models.
problem Improving accuracy of melting temperature prediction for protein fragments.
method Promoting sparsity in pre-trained transformer models and adopting probabilistic frameworks.
result Mean absolute error of 0.23C for predicting melting temperature.
Protein Thoughts interprets protein interactions with clear reasoning, improving prediction accuracy.
problem Lack of mechanistic justification in protein-protein interaction predictions.
method Interpretable search problem reformulation, hypothesis-guided entropy-regularized Tree-of-Thoughts search, embedding-space flow matching.
result Improves mean best-binder rank from 47.7 to 11.2 on SHS148k benchmark.
Predicting RNA base distances using a large language model.
problem Accurately predicting RNA structural information, especially distance maps.
method Using a large pretrained RNA language model coupled with a transformer.
result The model can accurately infer RNA base distances from sequence data.
New Performer model tackles long-sequence protein modeling.
problem Challenges of training complex Transformer models for long sequences.
method Linearly scalable long-context Transformer architecture, Performer.
result Performer provides strong theoretical guarantees and is effective for protein sequence modeling.
Branching Flows generates sequences of varying lengths using binary trees.
problem Generating sequences of unknown lengths or fixed elements.
method A generative modeling framework that evolves states over binary trees, controlling sequence length.
result Branching Flows can generate sequences of varying lengths and mix different types of state spaces.
LMI approximates mutual information in high dimensions using learned low-dimensional representations.
problem Estimating mutual information between high-dimensional variables is challenging due to sample size limitations.
method Developed a method called latent MI (LMI) approximation that applies a nonparametric MI estimator to low-dimensional representations learned by a simple model architecture.
result LMI can approximate MI well for variables with >10^3 dimensions if their dependence structure has low intrinsic dimensionality.
Deep learning models optimize protein sequences.
problem Optimizing protein properties through sequence design.
method Deep generative models guided by machine learning.
result Improved protein sequence generation from prior knowledge.
Proteins are commonly used by biochemical industry for numerous processes. Refining these proteins' properties via mutations causes stability effects as well. Accurate computational method to predict how mutations affect protein stability are necessary to facilitate efficient protein design. However, accuracy of predic…
EBM predicts protein conformations at atomic scale using crystallized data.
problem Predicting the conformation of a side chain from its context within a protein structure.
method Energy-based model trained on crystallized protein data, evaluating performance on rotamer recovery task.
result EBM achieves performance close to state-of-the-art methods, including Rosetta energy function.
Deep generative models have achieved remarkable success in various data domains, including images, time series, and natural languages. There remain, however, substantial challenges for combinatorial structures, including graphs. One of the key challenges lies in the difficulty of ensuring semantic validity in context. …
A new model explains protein interactions via electron delocalization.
problem Understanding how protein interactions affect each other.
method Quantized discrete differential geometry of n-simplices.
result Allosteric regulation follows from the model of interactions.
We introduce a new model of proteins, which extends and enhances the traditional graphical representation by associating a combinatorial object called a fatgraph to any protein based upon its intrinsic geometry. Fatgraphs can easily be stored and manipulated as triples of permutations, and these methods are therefore a…
New method steers protein design towards desired properties.
problem Challenges in designing proteins with specific structures and properties.
method Feynman-Kac framework applied to RFdiffusion models with guiding potentials.
result Significant improvement in predicted interface energetics and binder designability.
Flexible Kernels for Protein Property Prediction
problem Predicting protein properties from sparse experimental data
method Sequence kernels using evolutionary substitution matrices and local linearity
result Data-efficient models of protein property landscapes
A new diffusion model generates novel protein backbones without relying on pretrained networks.
problem Generating novel protein backbones without relying on pretrained networks.
method Developed a SE(3) invariant diffusion model on multiple frames, called FrameDiff.
result Generated designable protein monomers up to 500 amino acids without pretrained networks.
Few-step protein backbone generators reduce sampling time by over 20x.
problem Computational bottleneck in diffusion-based protein generation models.
method Score distillation adapted for protein backbone generation, combined with inference time noise modulation.
result Significant reduction in sampling time (20+ fold) while maintaining comparable performance.
A new machine-learned CG model predicts protein structures efficiently.
problem Developing a universal, computationally efficient protein simulation model.
method Combining deep learning with all-atom protein simulations to create a transferable CG force field.
result The model predicts protein structures, intermediates, and fluctuations efficiently.
Generative model designs highly designable proteins using geometric algebra.
problem Creating proteins with diverse and statistically accurate secondary structures.
method Introduced a geometric algebra flow matching model (FrameFlow) with Clifford Frame Attention (CFA) for protein backbone design.
result Achieved high designability, diversity, and novelty in protein backbone sampling.
DiAMoNDBack models protein backmapping from coarse-grained Cα traces.
problem Restoring all-atom details from coarse-grained protein representations.
method Autoregressive denoising diffusion model for residue-by-residue backmapping.
result Achieves state-of-the-art reconstruction performance in diverse applications.
The effective representation of proteins is a crucial task that directly affects the performance of many bioinformatics problems. Related proteins usually bind to similar ligands. Chemical characteristics of ligands are known to capture the functional and mechanistic properties of proteins suggesting that a ligand base…
Two proteins are homologous if they have a common evolutionary origin, and the binary classification problem is to identify proteins in a candidate set that are homologous to a particular native protein. The feature (explanatory) variables available for classification are various measures of similarity of proteins. The…
Method uses network biology to construct gene expression models for cancer.
problem Building models for cancer phenotypes using gene expression data.
method Unsupervised construction of computational graphs based on protein-protein networks.
result The method outperforms other models in cancer phenotype analysis.
Recently exciting progress has been made on protein contact prediction, but the predicted contacts for proteins without many sequence homologs is still of low quality and not very useful for de novo structure prediction. This paper presents a new deep learning method that predicts contacts by integrating both evolution…
A new framework uses text descriptions to improve protein design.
problem Lack of effective methods to incorporate textual descriptions in protein design.
method ProteinDT framework that combines text and protein structural information.
result ProteinDT significantly improves protein design accuracy and performance.
Experimental determination of protein function is resource-consuming. As an alternative, computational prediction of protein function has received attention. In this context, protein structural classification (PSC) can help, by allowing for determining structural classes of currently unclassified proteins based on thei…
Amino acid sequence portrays most intrinsic form of a protein and expresses primary structure of protein. The order of amino acids in a sequence enables a protein to acquire a particular stable conformation that is responsible for the functions of the protein. This relationship between a sequence and its function motiv…
Rapid progress in deep learning has spurred its application to bioinformatics problems including protein structure prediction and design. In classic machine learning problems like computer vision, progress has been driven by standardized data sets that facilitate fair assessment of new methods and lower the barrier to …
Motivation: Prediction of the interaction affinity between proteins and compounds is a major challenge in the drug discovery process. WideDTA is a deep-learning based prediction model that employs chemical and biological textual sequence information to predict binding affinity. Results: WideDTA uses four text-based inf…
We present a machine learning framework for modeling protein dynamics. Our approach uses L1-regularized, reversible hidden Markov models to understand large protein datasets generated via molecular dynamics simulations. Our model is motivated by three design principles: (1) the requirement of massive scalability; (2) t…
InteractionNet models noncovalent protein-ligand interactions with GNNs and explains predictions.
problem Modeling noncovalent protein-ligand interactions with graph neural networks.
method InteractionNet uses a GNN architecture with separated covalent and noncovalent convolution layers and layer-wise relevance propagation for explainability.
result InteractionNet successfully predicts noncovalent protein-ligand interactions with chemical relevance.
Structure learning in random fields has attracted considerable attention due to its difficulty and importance in areas such as remote sensing, computational biology, natural language processing, protein networks, and social network analysis. We consider the problem of estimating the probabilistic graph structure associ…
As high-throughput biological sequencing becomes faster and cheaper, the need to extract useful information from sequencing becomes ever more paramount, often limited by low-throughput experimental characterizations. For proteins, accurate prediction of their functions directly from their primary amino-acid sequences h…
The worldwide surge of multiresistant microbial strains has propelled the search for alternative treatment options. The study of Protein-Protein Interactions (PPIs) has been a cornerstone in the clarification of complex physiological and pathogenic processes, thus being a priority for the identification of vital compon…
Automated protein function prediction is a challenging problem with distinctive features, such as the hierarchical organization of protein functions and the scarcity of annotated proteins for most biological functions. We propose a multitask learning algorithm addressing both issues. Unlike standard multitask algorithm…
Mathematical pipeline identifies structural homology of knotted proteins.
problem Quantification and classification of protein structures, especially knotted proteins, require noise-free and complete data.
method Developed a geometric framework using persistent homology to analyze protein structures.
result Persistent homology accurately represents structural homology of knotted proteins and identifies geometric features of protein entanglement.
Deep model learns protein interfaces from high-order interactions.
problem Predicting protein interfaces from amino acid pairs.
method Graph neural networks and convolutional neural networks for 2D dense predictions.
result Our method consistently improves interface prediction performance.
Smoothed fitness landscape improves protein optimization.
problem Infeasibility of combinatorially large protein sequence space.
method Formulate protein fitness as a graph signal, smooth using Tikunov regularization, and optimize with Gibbs sampling.
result 2.5 fold fitness improvement over training set.
Continuous-depth Evoformer reduces protein folding prediction time and resource usage.
problem Efficient protein structure prediction with reduced computational costs.
method Continuous-depth formulation of Evoformer using Neural Ordinary Differential Equations (Neural ODEs).
result The continuous-time Evoformer achieves constant memory cost and improved efficiency.
Automated protein structure prediction from cryo-EM data.
problem Challenging to build atomic models from cryo-EM densities without prior structure.
method Uses GCN and LSTM to automate model building from amino acid identities and candidate locations.
result Automated approach reduces time and eliminates human intervention for protein structure determination.