Folding and aggregation of designed proteins.

  title={Folding and aggregation of designed proteins.},
  author={Ricardo A. Broglia and Guido Tiana and Samuela Pasquali and H. Eduardo Roman and E. Vigezzi},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  volume={95 22},
  • R. Broglia, G. Tiana, E. Vigezzi
  • Published 14 April 1998
  • Chemistry
  • Proceedings of the National Academy of Sciences of the United States of America
Protein aggregation is studied by following the simultaneous folding of two designed identical 20-letter amino acid chains within the framework of a lattice model and using Monte Carlo simulations. It is found that protein aggregation is determined by elementary structures (partially folded intermediates) controlled by local contacts among some of the most strongly interacting amino acids and formed at an early stage in the folding process. 
In silico evidence that protein unfolding is as a precursor of the protein aggregation.
We present a computational study on the folding and aggregation of proteins in an aqueous environment, as a function of its concentration.  We show how the increase of the concentration of individual
Competition between protein folding and aggregation: A three-dimensional lattice-model simulation
A Monte Carlo study of a multichain system of coarse-grained model proteins akin to lattice models developed for simulations of protein folding to examine the competition between intramolecular interactions leading to the native protein structure, and intermolecular association, resulting in the formation of aggregates of misfolded chains.
Coupled folding-binding versus docking: a lattice model study.
A Monte Carlo study of the thermodynamics and kinetics of binding to a target structure for two closely related sequences, one of which has a unique folded state while the other is unstructured, obtaining significant differences in their binding behavior.
Statistical analysis of native contact formation in the folding of designed model proteins
The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds
Design and folding of dimeric proteins
Dimerization is studied by following the evolution of two identical 20‐letter amino acid chains within the framework of a lattice model and using Monte Carlo simulations, and it is found that theory provides an overall account of the experimental findings.
Effect of secondary structure on protein aggregation: A replica exchange simulation study
Simulation studies of coarse-grained model oligopeptides that mimic aggregating proteins and a generalized Go model for a set of sequences with varying contents of secondary-structural motifs akin to α-helices and β-sheets are presented.
Clark Cooperative folders resist aggregation Protein aggregation determinants from a simplified model :
Two-chain aggregation simulations using minimalist models of proteins G, L, and mutants were used to investigate the fundamentals of protein aggregation and folding cooperativity stands out as the best single-chain determinant under these conditions and for these simple models.
Simple Model Study of Phase Transition Properties of Isolated and Aggregated Protein
We investigate the phase transition properties of isolated and aggregated protein by exhaustive numerical study in the confined conformation space with maximally compact lattice model. The study
The competition between protein folding and aggregation: off-lattice minimalist model studies.
Langevin dynamics simulations of minimalist model proteins show that multiple mechanisms for aggregation exist, but certain pathways are statistically preferred, and Kinetic data show that there are multiple time scales for aggregation, although most association events take place at times much shorter than those required for folding.
Replica exchange molecular dynamics simulations of amyloid peptide aggregation.
The replica exchange molecular dynamics (REMD) approach is applied to four oligomeric peptide systems and allows to compare the amyloidogenic propensity of different peptides.


Transient aggregates in protein folding are easily mistaken for folding intermediates.
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It is reported here that the rapidly formed intermediate of the spliceosomal protein U1A is an off-pathway artefact caused by transient aggregation of denatured protein under native conditions.
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It is shown that compaction is sufficient to create secondary structure, using simple nonlattice protein models, and the relative role of energy and entropy is examined.
Proteins with selected sequences fold into unique native conformation.
Results suggest that thermodynamically oriented selection of sequences which makes the native conformation a pronounced deep minimum of energy solves the problem of kinetic accessibility of this conformation as well.
Folding and misfolding of designed proteinlike chains with mutations
The analysis reveals that mutations affect primarily the energetics of the native conformation and to a much lesser extent the ensemble of unfolded conformations, corroborating the utility of the “energy gap” concept for the analysis of folding properties of proteinlike heteropolymers.
A lattice statistical mechanics model of the conformational and sequence spaces of proteins
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Folding and Association Versus Misfolding and Aggregation of Proteins
The acquisition of spatial structure in proteins may be described in terms of hierarchical condensation, with contributions of local interactions between next neighbours and the interactions between
Studies on protein folding, unfolding and fluctuations by computer simulation. I. The effect of specific amino acid sequence represented by specific inter-unit interactions.
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Equilibrium compact intermediates may be good models for transient intermediates formed during folding, and in some cases from the same protein under different conditions, may be significantly different.