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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 biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools.…

Biological Physics · Physics 2019-11-25 Frank Noé , Gianni De Fabritiis , Cecilia Clementi

The native structures of proteins, except for notable exceptions of intrinsically disordered proteins, in general take their most stable conformation in the physiological condition to maintain their structural framework so that their…

Biomolecules · Quantitative Biology 2021-10-26 Lyman Monroe , Daisuke Kihara

Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…

Populations and Evolution · Quantitative Biology 2017-05-24 Amy I. Gilson , Ahmee Marshall-Christensen , Jeong-Mo Choi , Eugene I. Shakhnovich

Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…

Biomolecules · Quantitative Biology 2007-05-23 Eric J. Deeds , Eugene I. Shakhnovich

Single molecule force spectroscopy provide details of the underlying energy surfaces of proteins which are essential to the understanding of their unfolding process. Recently, it has been observed experimentally that by pulling proteins in…

Statistical Mechanics · Physics 2009-11-13 R. Rajesh , D. Giri , I. Jensen , S. Kumar

The protein folding problem is stated and a list of properties that do not depend upon specific molecules is compiled and analyzed. The relationship of this analysis to future simulations is emphasized. The choice of power and time as…

Biological Physics · Physics 2017-09-26 Walter A. Simmons

Background: Genotype-phenotype maps provide a meaningful filtration of sequence space and RNA secondary structures are particular such phenotypes. Compatible sequences i.e.~sequences that satisfy the base pairing constraints of a given RNA…

Biomolecules · Quantitative Biology 2019-10-02 Fenix W. Huang , Christopher L. Barrett , Christian M. Reidys

Extensive Monte Carlo folding simulations for four proteins of various structural classes are carried out, using a single atomistic potential. In all cases, collapse occurs at a very early stage, and proteins fold into their native-like…

Statistical Mechanics · Physics 2009-11-10 Seung-Yeon Kim , Julian Lee , Jooyoung Lee

We recently introduced a physical model [Hoang et al., P. Natl. Acad. Sci. USA (2004), Banavar et al., Phys. Rev. E (2004)] for proteins which incorporates, in an approximate manner, several key features such as the inherent anisotropy of a…

Biomolecules · Quantitative Biology 2007-05-23 Trinh X. Hoang , Antonio Trovato , Flavio Seno , Jayanth R. Banavar , Amos Maritan

Over the years, advances in experimental and computational methods have helped us to understand the role of thermodynamic, kinetic and active (chaperone-aided) effects in coordinating the folding steps required to achieving a knotted native…

Biomolecules · Quantitative Biology 2016-10-20 Sophie E. Jackson , Antonio Suma , Cristian Micheletti

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding…

Quantitative Methods · Quantitative Biology 2018-08-14 Sneha Vishwanath , Alexandre De Brevern , Narayanaswamy Srinivasan

In the current AFM experiments the distribution of unfolding times, P(t), is measured by applying a constant stretching force f_s from which the apparent unfolding rate is obtained. To describe the complexity of the underlying energy…

Soft Condensed Matter · Physics 2009-11-11 V. Barsegov , D. Klimov , D. Thirumalai

Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is…

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

We solve a model that takes into account entropic barriers, frustration, and the organization of a protein-like molecule. For a chain of size $M$, there is an effective folding transition to an ordered structure. Without frustration, this…

Condensed Matter · Physics 2009-10-28 Carlos J. Camacho

We develop a path-based approach to continuous-time random walks on networks with arbitrarily weighted edges. We describe an efficient numerical algorithm for calculating statistical properties of the stochastic path ensemble. After…

Populations and Evolution · Quantitative Biology 2014-08-19 Michael Manhart , Alexandre V. Morozov

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling…

Biomolecules · Quantitative Biology 2010-07-05 Michael C. Prentiss , David J. Wales , Peter G. Wolynes

Statistical models for families of evolutionary related proteins have recently gained interest: in particular pairwise Potts models, as those inferred by the Direct-Coupling Analysis, have been able to extract information about the…

Biomolecules · Quantitative Biology 2019-09-25 Kai Shimagaki , Martin Weigt

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