22 papers · ranked by Valyu relevance
Federico A Olivieri, Alina Konstantinova, Neža Ribnikar, Nej Bizjak + 4 more
Over the past decade, protein design has evolved from a specialized discipline into a broadly accessible approach for engineering and interrogating biological systems. Despite these advances, protein design continues to be a technically challenging task, often requiring knowledge of programming to be able to use and…
Daniel T. Haas, Daniel Weindl, Pamela Kakimoto, Eva-Maria Trautmann + 9 more
Systematic proteomic organelle profiling methods including protein correlation profiling and LOPIT have advanced our understanding of cellular compartmentalization. To manage the complexity of organelle profiling data, we introduce C-COMPASS, a user-friendly open-source software that employs a neural network-based…
Sébastien Sueron, Sayyed Jalil Mahdizadeh, Eric Chevet, Xavier Guillory + 2 more
PROteolysis TArgeting Chimeras (PROTACs) are bifunctional molecules designed to induce targeted protein degradation by forming a transient ternary complex between an E3 ubiquitin ligase and a protein of interest (POI), leading to the E3-mediated ubiquitination of the POI and its subsequent proteasomal degradation.…
Adara Walker, Matthew J. Guberman-Pfeffer
Millions of experimental and AI-predicted protein structures are now available, and the biosynthetic promise of bespoke proteins is increasingly within reach. The functional characterization challenge thus posed cannot be addressed by experimental techniques alone. Molecular dynamics (MD) simulations offer functional…
Saahithi Vemuri, Laxmi Priya Bijigiri, Sanjana Gogte, Vani Kondaparthi
PROTACs work by bringing together a protein-of-interest ligand and an E3 ligase recruiter to trigger targeted degradation. However, Diffusion-based generative models frequently produce chemically invalid or disconnected linker structures that satisfy global geometric constraints but violate local bonding requirements.…
Marek Kokot, Amitava Roy, Travis J Wheeler, Sebastian Deorowicz
Molecular dynamics (MD) simulations model the physical movements of atoms in biomolecular systems over time, providing atomic-resolution insight into conformational changes, binding events, and dynamic behaviors that cannot be captured by static structures alone. As such, MD simulations are playing an increasingly…
Authors not listed
The functionality of viral proteases, such as those from Dengue Virus (DENV) and SARS-CoV-2, is intrinsically linked to their conformational dynamics. While Molecular Dynamics (MD) is a powerful tool to study these motions, its computational cost limits large-scale screening. Here, we present a rapid analysis of the…
Jürgen Bartel, Philipp T Kaulich, Borja Ferrero-Bordera, Rick Gelhausen + 4 more
In proteome studies, the application of alternative proteases, exclusively or in addition to trypsin, often increases protein sequence or proteome coverage. It has recently been shown that, in particular, the analysis of small proteins benefits from such multi-protease approaches. However, selecting the most optimal…
Danial Gharaie Amirabadi, Cody Jackson, Dong Su Kim, Maximilian Sprang + 1 more
Protein engineering often relies on separate models for related developability properties, limiting efficiency and transfer across tasks. We present Prot2Prop, a multitask framework based on a frozen ProstT5 encoder with shared and task-specific adapters for joint prediction of six protein properties: material…
Bryan Cheng, Austin Jin
Proteolysis-targeting chimeras (PROTACs) can selectively degrade disease-causing proteins, yet predicting which targets are amenable to degradation remains a critical bottleneck: existing computational methods require the complete PROTAC molecular structure, information unavailable before synthesis. We present…
Aditi T. Merchant, Daniel Guo, Ben Viggiano, Lucas Brennan-Almaraz + 6 more
Programmable composition of complex systems is a longstanding goal of biological research. Generative modeling has improved the reliability of computational design, but existing methods are highly specialized and are difficult to extend or compose. Here, we introduce Proto, a high-level programming language for…
Authors not listed
Fragment-based drug discovery (FBDD) is a widely used strategy in early-stage drug development, but accurately predicting the binding affinities of fragments and their elaborated analogs poses unique computational challenges. These difficulties arise from weak binding affinities, diverse chemical scaffolds, and limited…
Jingjie Zhang, Hanqun Cao, Zijun Gao, Yu Wang + 7 more
Post-translational modifications (PTMs) form a combinatorial "code" that regulates protein function, yet deciphering this code—linking modified sites to their catalytic enzymes—remains a central unsolved problem in understanding cellular signaling and disease. We introduce COMPASS-PTM, a mechanism-aware, coarse-to-fine…
Jordan C Rozum, Amy C Sims, Xiaolu Li, Snigdha Sarkar + 7 more
Systemic perturbations trigger extensive changes across the proteome-altering protein abundance, post-translational modifications (PTMs), conformational states, and complex assembly. Interpreting these effects demands computational pipelines capable of integrating diverse proteomics modalities, such as multi-PTM…
Yi Zhou, Haohao Qu, Yunqing Liu, Shanru Lin + 2 more
Proteins inherently possess a consistent sequence-structure duality. The abundance of protein sequence data, which can be readily represented as discrete tokens, has driven fruitful developments in protein language models (pLMs). A key remaining challenge, however, is how to effectively integrate continuous structural…
Leah V Schaffer, Mayank Jain, Rami Nasser, Roded Sharan + 2 more
ProteinProjector presents a flexible framework for integrating multiple proteomics data sources into a low dimensional representation of each protein which can be used for downstream analyses such as mapping subcellular structure. Alternative approaches (e.g. feature concatenation, [sup1] at Bioinformatics Advances…
Yunhyeok Lee, Jun Ren, Jingyu Lee, Minh Thi-Hong Tran + 5 more
In synthetic metabolic pathways, the intracellular level of enzymes is a critical determinant of pathway efficiency and, thus, short-lived enzymes create bottlenecks and limit overall metabolic productivity due to their low abundance. However, since studies on protein half-life remain limited in bacteria, its accurate…
Zheng Ma, Jiazhen Chen, Lei Xin, Ali Ghodsi
The integration of deep learning approaches in biomedical research has been transformative, enabling breakthroughs in various applications. Despite these strides, its application in protein inference is impeded by the scarcity of extensively labeled datasets, a challenge compounded by the high costs and complexities of…
Authors not listed
Cold regulated protein 15A (COR15A) is a late embryogenesis abundant (LEA) protein from Arabidopsis thaliana which is expressed in response to low temperatures and dehydration. Here we use a combination of ion mobility-mass spectrometry (IM-MS) and molecular dynamics (MD) simulations with elevated temperature for…
Authors not listed
Computational blind challenges offer critical, unbiased assessment opportunities to assess and accelerate scientific progress, as demonstrated by a breadth of breakthroughs over the last decade. We report the outcomes and key insights from an open science community blind challenge focused on computational methods in…
Tieu-Long Phan, Lai Hoang Son Le, Thanh-An Pham, Nhu-Ngoc Nguyen Song + 2 more
Protein--ligand docking is widely used in structure-based discovery, but routine studies often fail at the workflow level rather than at the scoring level. Receptor cleaning, ligand preparation, file conversion, box definition, run organization, and downstream parsing are frequently handled by fragmented scripts, which…
Authors not listed
Target-aware molecular generation models have emerged as promising tools for structure-based drug discovery, yet it remains unclear whether they genuinely exploit target information or merely resemble the Texas Sharpshooter fallacy by retrospectively rationalizing outputs. To address this, we introduce TarPass, a…