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Accurately determining a change in protein binding affinity upon mutations is important for the discovery and design of novel therapeutics and to assist mutagenesis studies. Determination of change in binding affinity upon mutations…

Biomolecules · Quantitative Biology 2021-09-01 Wajid Arshad Abbasi , Syed Ali Abbas , Saiqa Andleeb

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

We present a simple model of protein folding dynamics that captures key qualitative elements recently seen in all-atom simulations. The goals of this theory are to serve as a simple formalism for gaining deeper insight into the physical…

Biological Physics · Physics 2015-05-19 Vijay S. Pande

Characterization of protein energy landscape and conformational ensembles is important for understanding mechanisms of protein folding and function. We studied ensembles of bound and unbound conformations of six proteins to explore their…

Biological Physics · Physics 2012-11-06 Anatoly M. Ruvinsky , Tatsiana Kirys , Alexander V. Tuzikov , Ilya A. Vakser

Focusing on a small set of proteins that i) fold in a concerted, all-or-none fashion and ii) do not contain knots or slipknots, we show that the Gauss linking integral, the torsion and the number of sequence-distant contacts provide…

Quantitative Methods · Quantitative Biology 2019-10-01 E. Panagiotou , K. W. Plaxco

The folding dynamics of small single-domain proteins is a current focus of simulations and experiments. Many of these proteins are 'two-state folders', i.e. proteins that fold rather directly from the denatured state to the native state,…

Biomolecules · Quantitative Biology 2020-01-08 Thomas R. Weikl

The dynamics of a folded protein is studied in water and glycerol at a series of temperatures below and above their respective dynamical transition. The system is modeled in two distinct states whereby the protein is decoupled from the bulk…

Soft Condensed Matter · Physics 2008-09-23 C. Atilgan , A. O. Aykut , A. R. Atilgan

Enzyme-based systems have been shown to undergo directional motion in response to their substrate gradient. Here, we formulate a kinetic model to analyze the directional movement of an ensemble of protein molecules in response to a gradient…

Biological Physics · Physics 2021-03-26 Niladri Sekhar Mandal , Ayusman Sen

Model off-lattice sequences in two dimensions are constructed so that their native states are close to an on-lattice target. The Hamiltonian involves the Lennard-Jones and harmonic interactions. The native states of these sequences are…

Soft Condensed Matter · Physics 2009-10-31 Mai Suan Li , Marek Cieplak

The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the…

Soft Condensed Matter · Physics 2009-10-31 R. A Broglia , G. Tiana , H. E. Roman , E. Vigezzi , E. I. Shakhnovich

We investigate the folding behavior of protein sequences by numerically studying all sequences with maximally compact lattice model through exhaustive enumeration. We get the prion-like behavior of protein folding. Individual proteins…

Biomolecules · Quantitative Biology 2014-11-18 Yong-Yun Ji , You-Quan Li , Jun-Wen Mao , Xiao-Wei Tang

Binary fluorescence time series obtained from single-molecule imaging experiments can be used to infer protein binding kinetics, in particular, association and dissociation rate constants from waiting time statistics of fluorescence…

Quantitative Methods · Quantitative Biology 2012-06-15 Jin Yang , John E. Pearson

Making use of a simplified model for protein folding, it can be shown that conformations which are particularly stable when their energy is minimized with respect to amino acid sequence (in the sense that they display a large energy gap to…

Soft Condensed Matter · Physics 2007-05-23 R. A. Broglia , G. Tiana , H. E. Roman

Most widely used ligand docking methods assume a rigid protein structure. This leads to problems when the structure of the target protein deforms upon ligand binding. In particular, the ligand's true binding pose is often scored very…

Biomolecules · Quantitative Biology 2023-03-22 Patricia Suriana , Joseph M. Paggi , Ron O. Dror

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

Protein-ligand binding is essential to almost all life processes. The understanding of protein-ligand interactions is fundamentally important to rational drug design and protein design. Based on large scale data sets, we show that protein…

Biomolecules · Quantitative Biology 2017-04-21 Duc Duy Nguyen , Tian Xiao , Menglun Wang , Guo-Wei Wei

Molecular dynamics simulations of folding in an off-lattice protein model reveal a nucleation scenario, in which a few well-defined contacts are formed with high probability in the transition state ensemble of conformations. Their…

Statistical Mechanics · Physics 2009-09-25 Nikolay V. Dokholyan , Sergey V. Buldyrev , H. Eugene Stanley , Eugene I. Shakhnovich

The importance of torsion vibration in the transmission of life information is indicated. The localization of quantum torsion state is proved. Following these analyses a formalism on the quantum theory of conformation-electron system is…

Biomolecules · Quantitative Biology 2009-06-16 Liaofu Luo

We have used numerical simulations to investigate how the properties of motor proteins control the dynamical behavior of a driven flexible filament. The filament is pinned at one end and positioned on top of a patch of anchored motor…

Soft Condensed Matter · Physics 2024-09-20 Amir Khosravanizadeh , Serge Dmitrieff

We investigate the sequence-dependent properties of proteins that determine the dual requirements of stability of the native state and its kinetic accessibility using simple cubic lattice models. Three interaction schemes are used to…

Soft Condensed Matter · Physics 2009-10-31 D. K. Klimov , D. Thirumalai