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A general theoretical framework is developed using free energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from non-uniformity in native…

Disordered Systems and Neural Networks · Physics 2007-05-23 Steven S. Plotkin , Jose N. Onuchic

We present a simple physical model which demonstrates that the native state folds of proteins can emerge on the basis of considerations of geometry and symmetry. We show that the inherent anisotropy of a chain molecule, the geometrical and…

Biomolecules · Quantitative Biology 2009-11-10 Trinh Xuan Hoang , Antonio Trovato , Flavio Seno , Jayanth R. Banavar , Amos Maritan

Understanding how proteins fold into their native structure is a fundamental problem in biophysics, crucial for protein design. It has been hypothesized that the formation of a molten globule intermediate precedes folding to the native…

Soft Condensed Matter · Physics 2022-04-13 Marc Rico-Pasto , Annamaria Zaltron , Sebastian J. Davies , Silvia Frutos , Felix Ritort

We present a statistical mechanics treatment of the stability of globular proteins which takes explicitly into account the coupling between the protein and water degrees of freedom. This allows us to describe both the cold and the warm…

Condensed Matter · Physics 2009-10-30 Alex Hansen , Mogens H. Jensen , Kim Sneppen , Giovanni Zocchi

The near-native free energy landscape of protein G is investigated through 0.4 microseconds-long atomistic molecular dynamics simulations in explicit solvent. A theoretical and computational framework is used to assess the time-dependence…

Biomolecules · Quantitative Biology 2009-11-13 F. Pontiggia , G. Colombo , C. Micheletti , H. Orland

Inherent structure theory is used to discover strong connections between simple characteristics of protein structure and the energy landscape of a Go model. The potential energies and vibrational free energies of inherent structures are…

Biomolecules · Quantitative Biology 2009-11-13 Dengming Ming , Marian Anghel , Michael E. Wall

The folding ability of a heteropolymer model for proteins subject to Monte Carlo dynamics on a simple cubic lattice is shown to be strongly correlated with the energy gap between the native state and the structurally dissimilar part of the…

Condensed Matter · Physics 2007-05-23 Aaron R. Dinner , Victor Abkevich , Eugene Shakhnovich , Martin Karplus

The presence of metamorphism in the protein's native state is not yet fully understood. In an attempt to throw light on this issue here we present an assessment, in terms of the amide hydrogen exchange protection factor, that aims to…

Biomolecules · Quantitative Biology 2021-05-21 Jorge A. Vila

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can…

Disordered Systems and Neural Networks · Physics 2009-10-31 Steven S. Plotkin , Jose N. Onuchic

Exact and approximate formulas for the upper bound of the relative energy difference of two Gaussian states with the fixed fidelity between them are derived. The reciprocal formulas for the upper bound of the fidelity for the fixed value of…

Quantum Physics · Physics 2015-06-03 V. V. Dodonov

Predictions of relative stabilities of (competing) molecular crystals are of great technological relevance, most notably for the pharmaceutical industry. However, they present a long-standing challenge for modeling, as often minuscule free…

Materials Science · Physics 2022-05-25 Venkat Kapil , Edgar A Engel

We analytically derive the lower bound of the total conformational energy of a protein structure by assuming that the total conformational energy is well approximated by the sum of sequence-dependent pairwise contact energies. The condition…

Biomolecules · Quantitative Biology 2008-01-03 Akira R. Kinjo , Sanzo Miyazawa

The prediction of the biologically active native conformation of a protein is one of the fundamental challenges of structural biology. This problem remains yet unsolved mainly due to three factors: the partial knowledge of the effective…

Biomolecules · Quantitative Biology 2007-05-23 Jose Luis Alonso , Gregory A. Chass , Imre G. Csizmadia , Pablo Echenique , Alfonso Tarancon

The thermodynamic properties for three different types of off-lattice four-strand beta-sheet protein models interacting via a hybrid Go-type potential have been investigated. Discontinuous molecular dynamic simulations have been performed…

Biological Physics · Physics 2009-11-07 Hyunbum Jang , Carol K. Hall , Yaoqi Zhou

The fundamental law for protein folding is the Thermodynamic Principle: the amino acid sequence of a protein determines its native structure and the native structure has the minimum Gibbs free energy. If all chemical problems can be…

Biomolecules · Quantitative Biology 2012-04-10 Yi Fang

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

Current theories of heteropolymers are inherently macrpscopic, but are applied to folding proteins which are only mesoscopic. In these theories, one computes the averaged free energy over sequences, always assuming that it is self-averaging…

Soft Condensed Matter · Physics 2009-11-07 Jeffrey Chuang , Alexander Yu. Grosberg , Mehran Kardar

Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small fast folding proteins. To investigate the extent of the…

Statistical Mechanics · Physics 2007-05-23 Cecilia Clementi , Hugh Nymeyer , Jose' Nelson Onuchic

Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…

Biomolecules · Quantitative Biology 2017-03-16 Rocío Espada , R. Gonzalo Parra , Thierry Mora , Aleksandra M. Walczak , Diego U. Ferreiro

Scaling of folding times in Go models of proteins and of decoy structures with the Lennard-Jones potentials in the native contacts reveal %robust power law trends when studied under optimal folding conditions. The power law exponent depends…

Statistical Mechanics · Physics 2007-05-23 Marek Cieplak , Trinh Xuan Hoang
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