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Cooperativity is a hallmark of proteins, many of which show a modular architecture comprising discrete structural domains. Detecting and describing dynamic couplings between structural regions is difficult in view of the many-body nature of…

Biological Physics · Physics 2015-02-03 Olga Kononova , Lee Jones , Valeri Barsegov

We introduce a new nonlinear model for classification, in which we model the joint distribution of response variable, y, and covariates, x, non-parametrically using Dirichlet process mixtures. We keep the relationship between y and x linear…

Statistics Theory · Mathematics 2007-05-23 Babak Shahbaba , Radford M. Neal

In a shotgun proteomics experiment, proteins are the most biologically meaningful output. The success of proteomics studies depends on the ability to accurately and efficiently identify proteins. Many methods have been proposed to…

Quantitative Methods · Quantitative Biology 2012-11-30 Chao Yang , Zengyou He , Weichuan Yu

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

Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances both in theory and experiments have resulted in a conceptual framework for describing…

Soft Condensed Matter · Physics 2010-07-20 D. Thirumalai , Edward P. O'Brien , Greg Morrison , Changbong Hyeon

Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…

Biomolecules · Quantitative Biology 2023-11-13 A. Zambon , R. Zecchina , G. Tiana

Motivated by applications in protein function prediction, we consider a challenging supervised classification setting in which positive labels are scarce and there are no explicit negative labels. The learning algorithm must thus select…

Machine Learning · Computer Science 2019-01-28 Marco Frasca , Nicolò Cesa-Bianchi

This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy…

Biomolecules · Quantitative Biology 2014-01-06 N. P. Schafer , B. L. Kim , W. Zheng , P. G. Wolynes

We propose a general method for predicting potentially good folders from a given number of amino acid sequences. Our approach is based on the calculation of the rate of convergence of each amino acid chain towards the native structure using…

Biological Physics · Physics 2013-02-07 Dmitry K. Gridnev , Pedro Ojeda-May , Martin E. Garcia

The past decade has witnessed the development and success of coarse-grained network models of proteins for predicting many equilibrium properties related to collective modes of motion. Curiously, the results are usually robust towards the…

Biomolecules · Quantitative Biology 2010-02-04 Canan Atilgan , Osman Burak Okan , Ali Rana Atilgan

The prediction of the three-dimensional structures of the native state of proteins from the sequences of their amino acids is one of the most important challenges in molecular biology. An essential ingredient to solve this problem within…

Statistical Mechanics · Physics 2007-05-23 Cristian Micheletti , Flavio Seno , Jayanth Banavar , Amos Maritan

We employ simulations of model proteins to study folding on rugged energy landscapes. We construct ``first-passage'' networks as the system transitions from unfolded to native states. The nodes and bonds in these networks correspond to…

Soft Condensed Matter · Physics 2015-05-13 Gregg Lois , J. Blawzdziewicz , Corey S. O'Hern

To reduce experimental effort associated with directed protein evolution and to explore the sequence space encoded by mutating multiple positions simultaneously, we incorporate machine learning in the directed evolution workflow.…

Biomolecules · Quantitative Biology 2020-01-07 Zachary Wu , S. B. Jennifer Kan , Russell D. Lewis , Bruce J. Wittmann , Frances H. Arnold

A phenomenological model hamiltonian to describe the folding of a protein with any given sequence is proposed. The protein is thought of as a collection of pieces of helices; as a consequence its configuration space increases with the…

Soft Condensed Matter · Physics 2009-10-30 Pierpaolo Bruscolini

A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…

Biomolecules · Quantitative Biology 2018-08-09 William M. Jacobs , Eugene I. Shakhnovich

Studying evolutionary correlations in alignments of homologous sequences by means of an inverse Potts model has proven useful to obtain residue-residue contact energies and to predict contacts in proteins. The quality of the results depend…

Biomolecules · Quantitative Biology 2019-09-04 G. Franco , M. Cagiada , G. Bussi , G. Tiana

The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy Landscape Theory indicates that it is much easier to find sequences that satisfy the "Principle of Minimal…

Biomolecules · Quantitative Biology 2013-06-13 R. Gonzalo Parra , Rocío Espada , Ignacio E. Sánchez , Manfred J. Sippl , Diego U. Ferreiro

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

Folding and aggregation of proteins, the interaction between proteins and membranes, as well as the adsorption of organic soft matter to inorganic solid substrates belong to the most interesting challenges in understanding structure and…

Soft Condensed Matter · Physics 2007-12-06 Michael Bachmann , Wolfhard Janke

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated…