Defining the Nature of Thermal Intermediate in 3 State Folding Proteins: Apoflavodoxin, a Study Case

García-Fandiño, Rebeca; Bernadó, Pau; Ayuso-Tejedor, Sara; Sancho, Javier; Orozco, Modesto
August 2012
PLoS Computational Biology;Aug2012, Vol. 8 Issue 8, p1
Academic Journal
The early stages of the thermal unfolding of apoflavodoxin have been determined by using atomistic multi microsecondscale molecular dynamics (MD) simulations complemented with a variety of experimental techniques. Results strongly suggest that the intermediate is reached very early in the thermal unfolding process and that it has the properties of an ''activated'' form of the native state, where thermal fluctuations in the loops break loop-loop contacts. The unrestrained loops gain then kinetic energy corrupting short secondary structure elements without corrupting the core of the protein. The MD-derived ensembles agree with experimental observables and draw a picture of the intermediate state inconsistent with a well-defined structure and characteristic of a typical partially disordered protein. Our results allow us to speculate that proteins with a well packed core connected by long loops might behave as partially disordered proteins under native conditions, or alternatively behave as three state folders. Small details in the sequence, easily tunable by evolution, can yield to one or the other type of proteins.


Related Articles

  • Are the same or different amino acid residues responsible for correct and incorrect protein folding? Galzitskaya, O. V. // Biochemistry (00062979);Feb2009, Vol. 74 Issue 2, p186 

    It has been shown for 20 proteins that amino acid residues included into the protein folding nucleus, determined experimentally, are often involved in the theoretically determined amyloidogenic fragments. For 18 proteins, Φ-values indicative of the extent of residue involvement into the...

  • Understanding the Folding-Function Tradeoff in Proteins. Gosavi, Shachi // PLoS ONE;Apr2013, Vol. 8 Issue 4, p1 

    When an amino-acid sequence cannot be optimized for both folding and function, folding can get compromised in favor of function. To understand this tradeoff better, we devise a novel method for extracting the “function-less” folding-motif of a protein fold from a set of structurally...

  • Protein Structure Prediction using 2D HP Lattice Model Based on Integer Programming Approach. Mandal, Sayantan; Jana, Nanda Dulal // International Proceedings of Computer Science & Information Tech;2012, Vol. 38, p171 

    To predict structure of protein from primary amino acid sequence is computationally difficult. Protein folds on a lattice called conformation predict a native confirmation which has maximum topological hydrophobic contact. In this paper we address Integer Programming approach to predict protein...

  • Exploration of the relationship between topology and designability of conformations. Leelananda, Sumudu P.; Towfic, Fadi; Jernigan, Robert L.; Kloczkowski, Andrzej // Journal of Chemical Physics;6/21/2011, Vol. 134 Issue 23, p235101 

    Protein structures are evolutionarily more conserved than sequences, and sequences with very low sequence identity frequently share the same fold. This leads to the concept of protein designability. Some folds are more designable and lots of sequences can assume that fold. Elucidating the...

  • Predicting Protein Folds with Fold-Specific PSSM Libraries. Yoojin Hong; Chintapalli, Sree Vamsee; Kyung Dae Ko; Bhardwaj, Gaurav; Zhenhai Zhang; Rossum, Damian van; Patterson, Randen L. // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    Accurately assigning folds for divergent protein sequences is a major obstacle to structural studies. Herein, we outline an effective method for fold recognition using sets of PSSMs, each of which is constructed for different protein folds. Our analyses demonstrate that FSL (Fold-specific...

  • Neural Network Pairwise Interaction Fields for Protein Model Quality Assessment and Ab Initio Protein Folding. Martin, Alberto J. M.; Mirabello, Claudio; Pollastri, Gianluca // Current Protein & Peptide Science;Sep2011, Vol. 12 Issue 6, p549 

    In order to use a predicted protein structure one needs to know how good it is, as the utility of a model depends on its quality. To this aim, many Model Quality Assessment Programs (MQAP) have been developed over the last decade, with MQAP also being assessed at the CASP competition. We present...

  • The induction of α-helical structure in partially unfolded HypF-N does not affect its aggregation propensity. Ahmad, B.; Vigliotta, I.; Tatini, F.; Campioni, S.; Mannini, B.; Winkelmann, J.; Tiribilli, B.; Chiti, F. // PEDS: Protein Engineering, Design & Selection;Jul2011, Vol. 24 Issue 7, p553 

    The conversion of proteins into structured fibrillar aggregates is a central problem in protein chemistry, biotechnology, biology and medicine. It is generally accepted that aggregation takes place from partially structured states of proteins. However, the role of the residual structure present...

  • Role of Tryptophan Side Chain Dynamics on the Trp-Cage Mini-Protein Folding Studied by Molecular Dynamics Simulations. Kannan, Srinivasaraghavan; Zacharias, Martin // PLoS ONE;Feb2014, Vol. 9 Issue 2, p1 

    The 20 residue Trp-cage mini-protein is one of smallest proteins that adopt a stable folded structure containing also well-defined secondary structure elements. The hydrophobic core is arranged around a single central Trp residue. Despite several experimental and simulation studies the detailed...

  • Solvent effect on the folding dynamics and structure of E6-associated protein characterized from ab initio protein folding simulations. Xu, Zhijun; Lazim, Raudah; Sun, Tiedong; Mei, Ye; Zhang, Dawei // Journal of Chemical Physics;4/7/2012, Vol. 136 Issue 13, p135102 

    Solvent effect on protein conformation and folding mechanism of E6-associated protein (E6ap) peptide are investigated using a recently developed charge update scheme termed as adaptive hydrogen bond-specific charge (AHBC). On the basis of the close agreement between the calculated helix contents...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics