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We present and discuss a novel approach to the direct and inverse protein folding problem. The proposed strategy is based on a variational approach that allows the simultaneous extraction of amino acid interactions and the low-temperature…

Statistical Mechanics · Physics 2009-10-31 Flavio Seno , Cristian Micheletti , Amos Maritan , Jayanth R. Banavar

We study the ultrasensitivity of multisite binding processes where ligand molecules can bind to several binding sites, considering more particularly recent models involving complex chemical reactions in phosphorylation systems such as…

Subcellular Processes · Quantitative Biology 2016-05-02 Michaël Dougoud , Christian Mazza , Laura Vinckenbosch

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary…

Machine Learning · Computer Science 2026-05-26 Zhaohan Meng , Zhen Bai , Ke Yuan , Iadh Ounis , Zaiqiao Meng , Hao Xu , Joseph Loscalzo

Many processes in chemistry, physics, and biology involve rare events in which the system escapes from a metastable state by surmounting an activation barrier. Examples range from chemical reactions, protein folding, and nucleation events…

Chemical Physics · Physics 2020-10-07 Niels Zijlstra , Daniel Nettels , Rohit Satija , Dmitrii E. Makarov , Benjamin Schuler

Post-transductional modifications tune the functions of proteins and regulate the collective dynamics of biochemical networks that determine how cells respond to environmental signals. For example, protein phosphorylation and nitrosylation…

Cell Behavior · Quantitative Biology 2009-11-13 Roberto Chignola , Chiara Dalla Pellegrina , Alessio Del Fabbro , Edoardo Milotti

We analyze the efficiency of different methods for the calculation of reaction rates in the case of two simple analytical benchmark systems. Two classes of methods are considered: the first are based on the free energy calculation along a…

Statistical Mechanics · Physics 2009-11-11 Titus S. van Erp

In this paper we are interested in a degenerate parabolic system of reaction-diffusion equations arising in biology when studying cell adhesion at the protein level. In this modeling the unknown is the couple of the distribution laws of the…

Analysis of PDEs · Mathematics 2016-03-24 Philippe Grillot , Simona Mancini , Michèle Grillot

We develop a theory of reversible diffusion-controlled reactions with generalized binding/unbinding kinetics. In this framework, a diffusing particle can bind to the reactive substrate after a random number of arrivals onto it, with a given…

Chemical Physics · Physics 2023-10-03 Denis S. Grebenkov

We develop a broadly-applicable computational method for the automatic exploration of the bimolecular multi-reaction mechanism. The current methodology mainly involves the high-energy Born-Oppenheimer molecular dynamics (BOMD) simulation…

Chemical Physics · Physics 2021-12-24 Qinghai Cui , Jiawei Peng , Chao Xu , Zhenggang Lan

Transition state theory formally provides a simplifying approach for determining chemical reaction rates and pathways. Given an underlying potential energy surface for a reactive system, one can determine the dividing surface in phase space…

Empirical scoring functions based on either molecular force fields or cheminformatics descriptors are widely used, in conjunction with molecular docking, during the early stages of drug discovery to predict potency and binding affinity of a…

Machine Learning · Computer Science 2017-03-31 Joseph Gomes , Bharath Ramsundar , Evan N. Feinberg , Vijay S. Pande

Quantum tunneling reactions play a significant role in chemistry when classical pathways are energetically forbidden, be it in gas phase reactions, surface diffusion, or liquid phase chemistry. In general, such tunneling reactions are…

Chemical Physics · Physics 2023-03-28 Robert Wild , Markus Nötzold , Malcolm Simpson , Thuy Dung Tran , Roland Wester

We study the mechanical unfolding of a simple model protein. The Langevin dynamics results are analyzed using Markov-model methods which allow to describe completely the configurational space of the system. Using transition path theory we…

Biological Physics · Physics 2015-06-08 Rafael Tapia-Rojo , Sergio Arregui , Juan José Mazo , Fernando Falo

Amorphous oxide tunneling barriers, primarily formed from aluminum, represent one of the most widely adopted platforms for superconducting quantum bits (qubits). To overcome challenges associated with defects and sample variance among the…

Mesoscale and Nanoscale Physics · Physics 2025-12-23 Alexander C. Tyner , Alexander V. Balatsky

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. But despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high…

Biomolecules · Quantitative Biology 2022-09-28 John M McBride , Jean-Pierre Eckmann , Tsvi Tlusty

Designing novel proteins that bind to small molecules is a long-standing challenge in computational biology, with applications in developing catalysts, biosensors, and more. Current computational methods rely on the assumption that the…

Biomolecules · Quantitative Biology 2024-09-19 Junqi Liu , Shaoning Li , Chence Shi , Zhi Yang , Jian Tang

Transition path sampling is a method for estimating the rates of rare events in molecular systems based on the gradual transformation of a path distribution containing a small fraction of reactive trajectories into a biased distribution in…

Statistical Mechanics · Physics 2015-10-28 Pierre Terrier , Mihai-Cosmin Marinica , Manuel Athènes

We introduce a derangement model of ligand-receptor binding that allows us to quantitatively frame the question "How can ligands seek out and bind to their optimal receptor sites in a sea of other competing ligands and suboptimal receptor…

Biomolecules · Quantitative Biology 2022-08-24 Mobolaji Williams

The usual Kramers theory of reaction rates in a condensed medium predict the rate to have an $\eta^{-1}$ dependence, $\eta$ being the viscosity of the medium. However, experiments on ligand binding to proteins performed long ago, showed the…

Soft Condensed Matter · Physics 2019-06-18 K L Sebastian

A numerically effective procedure for determining weakly reversible chemical reaction networks that are linearly conjugate to a known reaction network is proposed in this paper. The method is based on translating the structural and…

Dynamical Systems · Mathematics 2014-07-15 Matthew D. Johnston , David Siegel , Gábor Szederkényi