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The ability to make zero-shot predictions about the fitness consequences of protein sequence changes with pre-trained machine learning models enables many practical applications. Such models can be applied for downstream tasks like genetic…

Quantitative Methods · Quantitative Biology 2025-04-24 Arnav Sharma , Anthony Gitter

A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical…

Biomolecules · Quantitative Biology 2009-11-13 Gregg Lois , Jerzy Blawzdziewicz , Corey S. O'Hern

Accurate estimation of mutational effects on protein-protein binding energies is an open problem with applications in structural biology and therapeutic design. Several deep learning predictors for this task have been proposed, but,…

Biomolecules · Quantitative Biology 2025-07-09 Arthur Deng , Karsten Householder , Fang Wu , Sebastian Thrun , K. Christopher Garcia , Brian Trippe

Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…

Biological Physics · Physics 2013-07-22 Ji Xu , Mengzhi Han , Ying Ren , Jinghai Li

We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wildtype structure after one or more random amino acid substitutions. Our theory predicts that for large numbers of…

Biomolecules · Quantitative Biology 2009-11-10 Jesse D. Bloom , Jonathan J. Silberg , Claus O. Wilke , D. Allan Drummond , Christoph Adami , Frances H. Arnold

Over the last 10-15 years a general understanding of the chemical reaction of protein folding has emerged from statistical mechanics. The lessons learned from protein folding kinetics based on energy landscape ideas have benefited protein…

Biomolecules · Quantitative Biology 2007-05-23 Michael C. Prentiss , Corey Hardin , Michael P. Eastwood , Chenghong Zong , Peter G. Wolynes

A computational method is developed to work on an inverse equilibrium problem with an interest towards applications with protein folding. In general, we are given a set of equilibrium confgiurations and want to derive the most probable…

Biological Physics · Physics 2007-05-23 John P. Donohue

Among the various features of amino acids, the hydrophobic property has most visible impact on stability of a sequence folding. This is mentioned in many protein folding related work, in this paper we more elaborately discuss the…

Computational Engineering, Finance, and Science · Computer Science 2013-12-16 Geetika Silakari Pandey , R. C. Jain

Directed evolution plays an indispensable role in protein engineering that revises existing protein sequences to attain new or enhanced functions. Accurately predicting the effects of protein variants necessitates an in-depth understanding…

Quantitative Methods · Quantitative Biology 2023-06-09 Yang Tan , Bingxin Zhou , Yuanhong Jiang , Yu Guang Wang , Liang Hong

Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure…

Quantitative Methods · Quantitative Biology 2020-05-19 Surbhi Dhingra , Ramanathan Sowdhamini , Frédéric Cadet , Bernard Offmann

Predicting the change in binding free energy ($\Delta \Delta G$) is crucial for understanding and modulating protein-protein interactions, which are critical in drug design. Due to the scarcity of experimental $\Delta \Delta G$ data,…

Computational Engineering, Finance, and Science · Computer Science 2024-10-15 Xiaoran Jiao , Weian Mao , Wengong Jin , Peiyuan Yang , Hao Chen , Chunhua Shen

We review the background, theory and general equations for the analysis of equilibrium protein unfolding experiments, focusing on denaturant and heat-induced unfolding. The primary focus is on the thermodynamics of reversible…

Biological Physics · Physics 2020-12-23 Kresten Lindorff-Larsen , Kaare Teilum

As an example of topic where biology and physics meet, we present the issue of protein folding and stability, and the development of thermodynamics-based bioinformatics tools that predict the stability and thermal resistance of proteins and…

Biomolecules · Quantitative Biology 2016-03-15 Fabrizio Pucci , Marianne Rooman

Zero-shot inference is a powerful paradigm that enables the use of large pretrained models for downstream classification tasks without further training. However, these models are vulnerable to inherited biases that can impact their…

Machine Learning · Computer Science 2024-02-13 Dyah Adila , Changho Shin , Linrong Cai , Frederic Sala

The statistical properties of protein folding within the {\phi}^4 model are investigated. The calculation is performed using statistical mechanics and path integral method. In particular, the evolution of heat capacity in term of…

Biological Physics · Physics 2013-09-03 M. Januar , A. Sulaiman , L. T. Handoko

This paper presents a method of reconstruction a primary structure of a protein that folds into a given geometrical shape. This method predicts the primary structure of a protein and restores its linear sequence of amino acids in the…

Quantitative Methods · Quantitative Biology 2017-01-04 Andrii Riazanov , Mikhail Karasikov , Sergei Grudinin

Inverse protein folding is challenging due to its inherent one-to-many mapping characteristic, where numerous possible amino acid sequences can fold into a single, identical protein backbone. This task involves not only identifying viable…

Quantitative Methods · Quantitative Biology 2023-11-08 Kai Yi , Bingxin Zhou , Yiqing Shen , Pietro Liò , Yu Guang Wang

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…

Soft Condensed Matter · Physics 2010-10-19 Pragya Shukla

In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…

Biological Physics · Physics 2018-11-26 Walter A. Simmons

The sensitivity of the native states of protein-like heteropolymers to mutations modelled as perturbations in the interaction potential between amino acids is studied. The stability threshold against mutations is shown to be zero for random…

Soft Condensed Matter · Physics 2009-10-30 Michele Vendruscolo , Amos Maritan , Jayanth R. Banavar
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