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Generating protein sequences conditioned on protein structures is an impactful technique for protein engineering. When synthesizing engineered proteins, they are commonly translated into DNA and expressed in an organism such as yeast. One…

Machine Learning · Computer Science 2024-09-27 Hannes Stark , Umesh Padia , Julia Balla , Cameron Diao , George Church

Protein function is driven by cohesive substructures, such as catalytic triads, binding pockets, and structural motifs, that occupy only a small fraction of a protein's residues. Yet existing pipelines built on protein encoders do not model…

Biomolecules · Quantitative Biology 2026-05-18 Xin Wang , Kaiwen Shi , Carlos Oliver

We propose a new and effective means for designing stable and fast-folding polypeptide sequences using a cumulant expansion of the molecular partition function. This method is unique in that $T_{Z}$, the ``cumulant design temperature''…

Condensed Matter · Physics 2007-05-23 Michael P. Morrissey , Eugene I. Shakhnovich

Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes…

Protein folding is one of the age-old biological problems that refers to the mechanism of understanding and predicting how a protein's linear sequence of amino acids folds into its specific three dimensional structure.This structure is…

De novo ligand design is a fundamental task that seeks to generate protein or molecule candidates that can effectively dock with protein receptors and achieve strong binding affinity entirely from scratch. It holds paramount significance…

Machine Learning · Computer Science 2025-10-13 Zekai Chen , Xunkai Li , Sirui Zhang , Henan Sun , Jia Li , Zhenjun Li , Bing Zhou , Rong-Hua Li , Guoren Wang

Recent advances in protein function prediction exploit graph-based deep learning approaches to correlate the structural and topological features of proteins with their molecular functions. However, proteins in vivo are not static but…

Biomolecules · Quantitative Biology 2022-11-22 Yuan Chiang , Wei-Han Hui , Shu-Wei Chang

The correct prediction of protein secondary structures is one of the key issues in predicting the correct protein folded shape, which is used for determining gene function. Existing methods make use of amino acids properties as indices to…

Quantitative Methods · Quantitative Biology 2017-05-01 Jian-Jun Shu , Kian-Yan Yong

These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…

Statistical Mechanics · Physics 2007-05-23 Jay Banavar , Amos Maritan , Cristian Micheletti , Flavio Seno

Molecular docking is a key computational tool utilized to predict the binding conformations of small molecules to protein targets, which is fundamental in the design of novel drugs. Despite recent advancements in geometric deep…

Biomolecules · Quantitative Biology 2023-12-01 Jiaxian Yan , Zaixi Zhang , Kai Zhang , Qi Liu

A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven different helix bundle proteins. The protocol, which includes…

Biomolecules · Quantitative Biology 2009-11-11 Isaac A. Hubner , Eric J. Deeds , Eugene I. Shakhnovich

Proteins tend to bury hydrophobic residues inside their core during the folding process to provide stability to the protein structure and to prevent aggregation. Nevertheless, proteins do expose some 'sticky' hydrophobic residues to the…

Biomolecules · Quantitative Biology 2021-07-27 Juami Hermine Mariama van Gils , Dea Gogishvili , Jan van Eck , Robbin Bouwmeester , Erik van Dijk , Sanne Abeln

The discovery of new materials has been the essential force which brings a discontinuous improvement to industrial products' performance. However, the extra-vast combinatorial design space of material structures exceeds human experts'…

The design of \emph{de novo} functional proteins that bind specific ligand molecules is paramount in therapeutics and bio-engineering. A critical yet formidable task in this endeavor is the design of the protein pocket, which is the cavity…

Biomolecules · Quantitative Biology 2023-10-23 Zaixi Zhang , Zepu Lu , Zhongkai Hao , Marinka Zitnik , Qi Liu

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

The folding of the cholesterol trapping apolipoprotein A1 in aqueous solution at increasing ionic strength is studied using atomically detailed molecular dynamics simulations. We calculate various structural properties to characterize the…

Soft Condensed Matter · Physics 2014-06-12 M. A. Balderas Altamirano , A. Gama Goicochea , E. Pérez

Cryo-electron microscopy (cryo-EM) is a technique for reconstructing the 3-dimensional (3D) structure of biomolecules (especially large protein complexes and molecular assemblies). As the resolution increases to the near-atomic scale,…

Computer Vision and Pattern Recognition · Computer Science 2023-08-08 Weijie Chen , Xinyan Wang , Yuhang Wang

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

Construction of a scaffold structure that supports a desired motif, conferring protein function, shows promise for the design of vaccines and enzymes. But a general solution to this motif-scaffolding problem remains open. Current…

Biomolecules · Quantitative Biology 2023-03-21 Brian L. Trippe , Jason Yim , Doug Tischer , David Baker , Tamara Broderick , Regina Barzilay , Tommi Jaakkola

Protein function is executed at the molecular surface, where shape and chemistry act together to govern interaction. Yet most comparison methods treat these aspects separately, privileging either global fold or local descriptors and missing…

Biomolecules · Quantitative Biology 2026-03-11 Himanshu Swami , John M. McBride , Jean-Pierre Eckmann , Tsvi Tlusty