Researchers identify critical protein residues using advanced graph theory.
problem Identifying essential residues in proteins for function.
method Learning Random Geometric Graphs (RGG) with Cramer's V correlation and organic thresholding.
result Advanced RGG methods accurately identify critical residues compared to existing techniques.
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.
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.
Motivation. Protein contact map describes the pairwise spatial and functional relationship of residues in a protein and contains key information for protein 3D structure prediction. Although studied extensively, it remains very challenging to predict contact map using only sequence information. Most existing methods pr…
Protein contacts contain important information for protein structure and functional study, but contact prediction from sequence remains very challenging. Both evolutionary coupling (EC) analysis and supervised machine learning methods are developed to predict contacts, making use of different types of information, resp…
GEFA predicts drug-target affinity using graph neural networks.
problem Accurate prediction of drug-target interactions for rapid drug repurposing.
method GEFA (Graph Early Fusion Affinity) is a novel graph-in-graph neural network with attention mechanism.
result GEFA effectively models drug-target interactions, demonstrating the effectiveness of pre-trained protein embedding and nested graph representation.
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.
Artificial neural networks (ANNs) have gained a well-deserved popularity among machine learning tools upon their recent successful applications in image- and sound processing and classification problems. ANNs have also been applied for predicting the family or function of a protein, knowing its residue sequence. Here w…
Recent developments in specialized computer hardware have greatly accelerated atomic level Molecular Dynamics (MD) simulations. A single GPU-attached cluster is capable of producing microsecond-length trajectories in reasonable amounts of time. Multiple protein states and a large number of microstates associated with f…
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…
Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for understanding function. Existing approaches for detecting structural similarity between prot…
Motivation: Proteins are known to undergo conformational changes in the course of their functions. The changes in conformation are often attributable to a small fraction of residues within the protein. Therefore identification of these variable regions is important for an understanding of protein function. Results: We …
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.
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.
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.
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…
A new method estimates protein evolutionary fields and couplings from alignments.
problem Estimating evolutionary fields and couplings from protein sequence alignments.
method Boltzmann machine with parallel, persistent Markov chain Monte Carlo method.
result Improved precision in predicting contact residue pairs.
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…
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.
Probabilistic principal component analysis (PPCA) seeks a low dimensional representation of a data set in the presence of independent spherical Gaussian noise. The maximum likelihood solution for the model is an eigenvalue problem on the sample covariance matrix. In this paper we consider the situation where the data v…
An invariant for knots with colored bonds respects HOMFLYPT relation.
problem Modeling and distinguishing knots with colored bonds.
method Introducing a HOMFLYPT skein module for colored bonded knots.
result The non-rigid version of the module provides information about knottedness of bonds.
ESS-Flow guides flow models without retraining, using Bayesian inference in source space.
problem Training flow models on paired data for conditional generation or sample production.
method Gradient-free Bayesian inference in source space using Elliptical Slice Sampling.
result Effective in diverse tasks including material design and protein structure prediction.
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…
New methods avoid spectral pollution in transfer operators for accurate analysis.
problem Spectral pollution in finite-dimensional approximations of transfer operators.
method Algorithms for computing spectral properties of transfer operators without spectral pollution.
result Accurate spectral estimation across various applications, including protein folding models.
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.
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.
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.
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.
New 3D protein analysis methods improve accuracy.
problem Lack of suitable learning algorithms for protein data.
method Intrinsic-Extrinsic Convolution and Pooling for 3D protein structures.
result Outperforms state-of-the-art methods on protein analysis tasks.
New method detects and compares folding pathways of knotted proteins.
problem Understanding the function of knots in protein folding.
method Topological analysis of protein knotoid distributions and entanglement.
result Reveals unique folding pathway for shallow knotted Carbonic Anhydrases.
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…
Improved protein structure classification using weighted graphlets and deep neural networks.
problem Protein structure classification for function prediction.
method Developed a weighted network and graphlet-based measure, combined with a deep neural network.
result Significantly improved performance on 36 real datasets compared to existing methods.
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.
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.
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.
Knot theory applied to proteins, distinguishing folded linear chains.
problem Classifying proteins as unknots when intra-chain interactions are ignored.
method Developing knot theory for folded linear molecular chains, considering self-bonding, and using Gauss codes and quandles.
result Extended knot theory to distinguish topologies of proteins with intra-chain bonds.
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…
Protein interactions constitute the fundamental building block of almost every life activity. Identifying protein communities from Protein-Protein Interaction (PPI) networks is essential to understand the principles of cellular organization and explore the causes of various diseases. It is critical to integrate multipl…
Mathematician summarizes protein geometry and mutation effects.
problem Understanding how proteins mutate and their structure-function relationship.
method Mathematical analysis of protein structures and functions, focusing on hydrogen bonds and secondary structure.
result Protein secondary structure regulates mutation by stabilizing or destabilizing regions.
Machine learning predicts protein structures and simulates dynamics.
problem Understanding and predicting protein folding and dynamics.
method Machine learning techniques for structure prediction and simulation.
result Machine learning enhances protein simulation and structure prediction.
EGR refines and assesses protein complex structures.
problem Improving the accuracy of protein complex 3D structures for drug discovery.
method E(3)-equivariant graph neural network (GNN) for multi-task refinement and assessment.
result EGR achieves state-of-the-art performance in refining and assessing protein complexes.
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…
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…
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
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.
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.
PLUS pre-trains protein sequences with structural info, improving performance.
problem Lack of labeled protein sequences for training models.
method PLUS combines masked language modeling with same-family prediction for pre-training.
result PLUS-RNN outperforms other models in protein biology tasks.
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.