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Understanding the principles of protein folding is a cornerstone of computational biology, with implications for drug design, bioengineering, and the understanding of fundamental biological processes. Lattice protein folding models offer a…

Disordered Systems and Neural Networks · Physics 2025-08-08 Shoummo Ahsan Khandoker , Estelle M. Inack , Mohamed Hibat-Allah

Designing protein mutants of both high stability and activity is a critical yet challenging task in protein engineering. Here, we introduce PRIME, a deep learning model, which can suggest protein mutants of improved stability and activity…

This paper presents a novel Differential Evolution algorithm for protein folding optimization that is applied to a three-dimensional AB off-lattice model. The proposed algorithm includes two new mechanisms. A local search is used to improve…

Artificial Intelligence · Computer Science 2018-05-08 Borko Bošković , Janez Brest

Accurate protein structure prediction from amino-acid sequences is critical to better understanding the protein function. Recent advances in this area largely benefit from more precise inter-residue distance and orientation predictions,…

Machine Learning · Computer Science 2021-06-01 Jiaxiang Wu , Shitong Luo , Tao Shen , Haidong Lan , Sheng Wang , Junzhou Huang

Protein evolution through amino acid mutations is a cornerstone of life sciences. Recent advances in protein language models have shown rich evolutionary patterns, offering unprecedented potential for in-silicon directed evolution. However,…

Artificial Intelligence · Computer Science 2026-01-08 Yaodong Yang , Yang Wang , Jinpeng Li , Pei Guo , Da Han , Guangyong Chen , Pheng-Ann Heng

The primary objective of most lead optimization campaigns is to enhance the binding affinity of ligands. For large molecules such as antibodies, identifying mutations that enhance antibody affinity is particularly challenging due to the…

Machine Learning · Computer Science 2024-06-12 Alexandra Gessner , Sebastian W. Ober , Owen Vickery , Dino Oglić , Talip Uçar

Accurate prediction and optimization of protein-protein binding affinity is crucial for therapeutic antibody development. Although machine learning-based prediction methods $\Delta\Delta G$ are suitable for large-scale mutant screening,…

Biomolecules · Quantitative Biology 2024-09-19 Kairi Furui , Masahito Ohue

Writing high-performance code requires significant expertise in the programming language, compiler optimizations, and hardware knowledge. This often leads to poor productivity and portability and is inconvenient for a non-programmer…

Performance · Computer Science 2020-09-01 Ajitesh Srivastava , Naifeng Zhang , Rajgopal Kannan , Viktor K. Prasanna

A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The…

Condensed Matter · Physics 2009-11-10 Ole Winther , Anders Krogh

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…

Machine Learning · Computer Science 2025-09-29 Hanqun Cao , Xinyi Zhou , Zijun Gao , Chenyu Wang , Xin Gao , Zhi Zhang , Cesar de la Fuente-Nunez , Chunbin Gu , Ge Liu , Pheng-Ann Heng

Directed evolution is a molecular biology technique that is transforming protein engineering by creating proteins with desirable properties and functions. However, it is experimentally impossible to perform the deep mutational scanning of…

Biomolecules · Quantitative Biology 2023-06-09 Yuchi Qiu , Guo-Wei Wei

Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact and clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel…

Motivation: Ab initio protein docking represents a major challenge for optimizing a noisy and costly "black box"-like function in a high-dimensional space. Despite progress in this field, there is no docking method available for rigorous…

Biomolecules · Quantitative Biology 2019-02-04 Yue Cao , Yang Shen

Protein fitness optimization is challenged by a vast combinatorial landscape where high-fitness variants are extremely sparse. Many current methods either underperform or require computationally expensive gradient-based sampling. We present…

Solving partial differential equations (PDEs) is a fundamental problem in science and engineering. While neural PDE solvers can be more efficient than established numerical solvers, they often require large amounts of training data that is…

Machine Learning · Computer Science 2025-03-25 Daniel Musekamp , Marimuthu Kalimuthu , David Holzmüller , Makoto Takamoto , Mathias Niepert

Evolutionary agentic systems intensify the trade-off between computational efficiency and reasoning capability by repeatedly invoking large language models (LLMs) during inference. This setting raises a central question: how can an agent…

Computation and Language · Computer Science 2026-04-27 Pretam Ray , Pratik Prabhanjan Brahma , Zicheng Liu , Emad Barsoum

We propose a new way of looking at global optimization of off-lattice protein models. We present a dual optimization concept of predicting optimal sequences as well as optimal folds. We validate the utility of the recently introduced…

Computational Physics · Physics 2012-05-22 István Kolossváry , Kevin J. Bowers

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Machine Learning · Computer Science 2023-09-19 Vijay Arvind. R , Haribharathi Sivakumar , Brindha. R

This paper presents a two-phase protein folding optimization on a three-dimensional AB off-lattice model. The first phase is responsible for forming conformations with a good hydrophobic core or a set of compact hydrophobic amino acid…

Neural and Evolutionary Computing · Computer Science 2020-06-30 Borko Bošković , Janez Brest

Domain-specific adaptation is critical to maximizing the performance of pre-trained language models (PLMs) on one or multiple targeted tasks, especially under resource-constrained use cases, such as edge devices. However, existing methods…

Computation and Language · Computer Science 2024-10-25 Peter Schafhalter , Shun Liao , Yanqi Zhou , Chih-Kuan Yeh , Arun Kandoor , James Laudon
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