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.
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.
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.
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 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.
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.
PGEL learns embeddings to diversify protein motifs while maintaining biological function.
problem Generating diverse protein structures while preserving biological function.
method Embedding learning framework that enhances motif diversity in a diffusion model's frozen denoiser.
result PGEL achieves greater structural diversity, better designability, and improved self-consistency compared to partial diffusion.
A faster method for optimizing DNA and protein sequences using machine learning.
problem Designing DNA and protein sequences with improved function.
method Activation maximization with a straight-through approximation and adaptive entropy variable.
result Fast SeqProp achieves up to 100-fold faster convergence and improved fitness optima.
BoGA combines evolutionary search with Bayesian optimization for efficient protein design.
problem Designing novel proteins with specific characteristics is challenging due to sequence space complexity.
method BoGA integrates a genetic algorithm with Bayesian optimization to efficiently explore sequence space.
result BoGA accelerates discovery of high-confidence binders for diverse protein design objectives.
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.
Improved scaffold generation for protein motifs using SE(3) flow matching.
problem Lack of structural diversity in generated scaffolds for protein motifs.
method Extended FrameFlow for motif-scaffolding with motif amortization and motif guidance.
result 2.5 times more designable and unique motif-scaffolds compared to state-of-the-art.
Unified model learns from proteins and ligands for drug design.
problem Disjoint data sources and modeling assumptions limit joint use of structure- and ligand-based drug design.
method Contrastive Geometric Learning for Unified Computational Drug Design (ConGLUDe)
result Unified model achieves competitive zero-shot virtual screening performance and state-of-the-art ligand-conditioned pocket selection.
New method learns diverse protein scaffolds for motif design.
problem Designing long, diverse protein scaffolds for specific motifs.
method E(3)-equivariant graph neural network for diffusion modeling.
result First to guarantee conditional sampling from diffusion models.
CogMol designs novel drug-like molecules for SARS-CoV-2 targets.
problem Designing efficient drugs for novel viral proteins.
method End-to-end framework combining VAE, controlled sampling, and predictors.
result Highly selective and affinity molecules for SARS-CoV-2 targets.
We present a new method for design problems wherein the goal is to maximize or specify the value of one or more properties of interest. For example, in protein design, one may wish to find the protein sequence that maximizes fluorescence. We assume access to one or more, potentially black box, stochastic "oracle" predi…
Geometric vector perceptrons improve protein structure learning.
problem Learning from protein structure with efficient and natural representations.
method Introducing geometric vector perceptrons to extend dense layers for Euclidean vectors, integrating geometric and relational reasoning.
result Improves model quality assessment and computational protein design over existing methods.
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…
Framework designs antiviral drugs using deep learning and RL.
problem Designing effective antiviral drugs for SARS-CoV-2.
method Deep learning framework with conditional molecular generator and RL.
result Framework generates more antiviral ligands than a VAE baseline.
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
Protein-ligand scoring is an important step in a structure-based drug design pipeline. Selecting a correct binding pose and predicting the binding affinity of a protein-ligand complex enables effective virtual screening. Machine learning techniques can make use of the increasing amounts of structural data that are beco…
Persistent homology provides a new, efficient molecular descriptor for protein dynamics.
problem Designing effective molecular descriptors for high-dimensional MD trajectories.
method Introduced masked Flood complex, a protein-tailored modification of simplicial complexes, for persistent homology.
result Persistent homology-based descriptors are competitive across protein dynamics tasks, including frame-level observable regression and MSM estimation.
DFMs enable flow-based models for multimodal discrete and continuous data.
problem Combining discrete and continuous data for generative models.
method Discrete Flow Models (DFMs) using Continuous Time Markov Chains.
result DFMs achieve state-of-the-art co-design performance for protein structure and sequence generation.
New method refines model predictions as design evolves.
problem Designing objects with desired properties using data-driven methods.
method Formalized as a game, developed autofocusing strategy for model retraining.
result Autofocusing improves model predictions in design space.
Non-autoregressive method speeds up protein folding prediction 23 times.
problem Generating protein sequences with higher order interactions.
method Discrete diffusion conditioned on 3D structure using ProteinMPNN.
result 23 times speed up in inference without performance loss.
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…
RG-VFM extends VFM to curved manifolds for better material and protein design.
problem Designing materials and proteins on curved manifolds.
method Riemannian Gaussian Variational Flow Matching (RG-VFM) for generative modeling on manifolds.
result RG-VFM more effectively captures manifold structure and improves performance.
The paper proposes a method to reliably select design algorithms for machine learning-guided design tasks.
problem Choosing the right design algorithm for machine learning-guided design tasks.
method Combining designs' predicted property values with held-out labeled data to reliably forecast characteristics of the label distributions produced by different design algorithms.
result The method is guaranteed to return design algorithms that yield successful label distributions.
SILVR generates new molecules fitting protein binding sites.
problem Generating novel small molecule compounds for drug design.
method Selective Iterative Latent Variable Refinement (SILVR) for diffusion-based molecule generation.
result SILVR can generate new molecules similar in shape to original fragments without protein knowledge.
Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools. The way simulations are performed to explore the energy landscape of protein sys…
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.
PANDA predicts protein binding affinity changes from sequences, outperforming existing methods.
problem Accurately predicting changes in protein binding affinity due to mutations.
method Sequence-based machine learning approach using protein sequence information.
result PANDA achieves higher Pearson correlation coefficients than existing methods.
We propose a novel transfer learning approach for orphan screening called corresponding projections. In orphan screening the learning task is to predict the binding affinities of compounds to an orphan protein, i.e., one for which no training data is available. The identification of compounds with high affinity is a ce…
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.
New tools evaluate and optimize conditional sequence models in bioinformatics.
problem Evaluating and optimizing conditional sequence models in bioinformatics.
method Kernel-based discrepancy measure (ACMMD) to estimate model fit and tune hyperparameters.
result Rejects the hypothesis that ProteinMPNN fits its data for various protein families and optimizes model temperature.
PropEn uses matching to create a larger dataset for efficient design optimization.
problem Limited data and complex landscapes in scientific applications.
method PropEn uses a matching approach to implicitly guide design without a discriminator.
result PropEn efficiently approximates the gradient of property improvement within the data distribution.
A novel framework refines diffusion models iteratively for better downstream reward optimization.
problem Optimizing reward functions during inference of diffusion models.
method Iterative refinement process with noising and reward-guided denoising steps.
result Superior empirical performance in protein and DNA design.
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.
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 …
Computational approaches to drug discovery can reduce the time and cost associated with experimental assays and enable the screening of novel chemotypes. Structure-based drug design methods rely on scoring functions to rank and predict binding affinities and poses. The ever-expanding amount of protein-ligand binding an…
The understanding of the type of inhibitory interaction plays an important role in drug design. Therefore, researchers are interested to know whether a drug has competitive or non-competitive interaction to particular protein targets. Method: to analyze the interaction types we propose factorization method Macau which …
Novel parallel GNN predicts protein-ligand interactions with high accuracy.
problem Accurate prediction of protein-ligand interactions for drug design.
method Parallel Graph Neural Networks (GNN) integrating 3D structural data.
result GNN achieves high accuracy in predicting binary interactions and activity.
Proteins are the major building blocks of life, and actuators of almost all chemical and biophysical events in living organisms. Their native structures in turn enable their biological functions which have a fundamental role in drug design. This motivates predicting the structure of a protein from its sequence of amino…
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.
GCPNet improves molecular graph learning for protein structure and binding.
problem Learning from 3D molecular graphs for protein structure and binding.
method SE(3)-equivariant graph neural network for 3D molecular graphs.
result GCPNet achieves state-of-the-art performance in multiple molecular tasks.
A new framework for controllable generation of discrete masked models.
problem Efficient controllable generation of discrete data models.
method Plug-and-play framework based on importance sampling.
result Demonstrates versatility across multiple domains, including protein design.
A deep neural network based architecture was constructed to predict amino acid side chain conformation with unprecedented accuracy. Amino acid side chain conformation prediction is essential for protein homology modeling and protein design. Current widely-adopted methods use physics-based energy functions to evaluate s…
Deep generative model discovers inhibitors for unknown targets.
problem Discovering novel inhibitor molecules for unknown drug targets.
method Deep generative framework trained on protein sequences, small molecules, and interactions.
result Micromolar-level inhibition observed for two out of four synthesized candidates, including activity against SARS-CoV-2 variants.
Researchers infer gene activity in dividing cells, accounting for protein inheritance and division history.
problem Inferring protein production kinetics in dividing cells due to protein inheritance and division history.
method Adapted conditional normalizing flows to approximate intractable likelihoods from simulated data.
result Glc3 gene is mostly inactive under stress, with brief and transient expression.