Special Issue "Protein Folding and Misfolding"

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A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (27 December 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Alexeii Finkelstein
Laboratory of Protein Physics, Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia
Website: http://phys.protres.ru/afinkel.html
E-Mail: afinkel@vega.protres.ru
Phone: +7 095 632 78 71
Interests: protein physics; theoretical investigations of protein folding; molecular physics; molecular biology; biochemistry; biocomputing; protein engineering introduction

Special Issue Information

Dear Colleagues,

The ability of protein chains to spontaneously form their spatial structures was a long-standing puzzle in molecular biology, especially because the measured rates of spontaneous folding range from microseconds to hours: the difference (at least 11 orders of magnitude) is akin to the difference between the life span of a mosquito and the age of the universe. Now, when this puzzle is solved in its basics, the main interest has been shifted (1) to the "natively disordered" proteins, which usually obtain their definite structure only when interact with target molecules, and (2) to the ability of many protein chains to form not only the "native" (properly working) 3D structures, but also the other ("misfolded") structures, which is also often connected with interaction of these chains with the other molecules.

These reconstructions of protein structures sometimes cause deadly diseases, and therefore the problem of protein folding and misfolding attains a great medical interest. Many new challenges are waiting in the field.

To illustrate for the readers of “Biomolecules” the importance of the protein folding and misfolding problem as a multidisciplinary field of research, this special issue is intended to show the various aspects of protein folding, misfolding and unfolding.

We look forward to reading your contributions,

Prof. Dr. Alexei Finkelsteint
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • protein folding
  • protein misfolding
  • protein unfolding
  • protein structure
  • natively disordered proteins
  • protein structure reconstruction
  • protein physics
  • protein engineering

Published Papers (21 papers)

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Displaying article 1-21
p. 956-979
by , ,  and
Biomolecules 2014, 4(4), 956-979; doi:10.3390/biom4040956
Received: 5 February 2014; in revised form: 29 August 2014 / Accepted: 19 September 2014 / Published: 20 October 2014
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(This article belongs to the Special Issue Protein Folding and Misfolding)
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p. 725-773
by  and
Biomolecules 2014, 4(3), 725-773; doi:10.3390/biom4030725
Received: 4 February 2014; in revised form: 17 June 2014 / Accepted: 20 June 2014 / Published: 24 July 2014
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(This article belongs to the Special Issue Protein Folding and Misfolding)
p. 498-509
by  and
Biomolecules 2014, 4(2), 498-509; doi:10.3390/biom4020498
Received: 28 February 2014; in revised form: 11 April 2014 / Accepted: 25 April 2014 / Published: 6 May 2014
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p. 458-473
by , ,  and
Biomolecules 2014, 4(2), 458-473; doi:10.3390/biom4020458
Received: 10 September 2013; in revised form: 28 March 2014 / Accepted: 2 April 2014 / Published: 22 April 2014
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(This article belongs to the Special Issue Protein Folding and Misfolding)
p. 354-373
by  and
Biomolecules 2014, 4(1), 354-373; doi:10.3390/biom4010354
Received: 31 December 2013; in revised form: 19 February 2014 / Accepted: 23 February 2014 / Published: 18 March 2014
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(This article belongs to the Special Issue Protein Folding and Misfolding)
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p. 291-314
by
Biomolecules 2014, 4(1), 291-314; doi:10.3390/biom4010291
Received: 25 December 2013; in revised form: 13 February 2014 / Accepted: 14 February 2014 / Published: 7 March 2014
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p. 268-288
by , ,  and
Biomolecules 2014, 4(1), 268-288; doi:10.3390/biom4010268
Received: 6 December 2013; in revised form: 11 February 2014 / Accepted: 13 February 2014 / Published: 27 February 2014
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p. 252-267
by , , ,  and
Biomolecules 2014, 4(1), 252-267; doi:10.3390/biom4010252
Received: 17 January 2014; in revised form: 14 February 2014 / Accepted: 19 February 2014 / Published: 25 February 2014
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p. 235-251
by  and
Biomolecules 2014, 4(1), 235-251; doi:10.3390/biom4010235
Received: 12 December 2013; in revised form: 23 January 2014 / Accepted: 10 February 2014 / Published: 20 February 2014
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p. 202-216
by
Biomolecules 2014, 4(1), 202-216; doi:10.3390/biom4010202
Received: 6 January 2014; in revised form: 5 February 2014 / Accepted: 10 February 2014 / Published: 13 February 2014
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p. 160-180
by ,  and
Biomolecules 2014, 4(1), 160-180; doi:10.3390/biom4010160
Received: 24 December 2013; in revised form: 22 January 2014 / Accepted: 30 January 2014 / Published: 10 February 2014
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p. 181-201
by  and
Biomolecules 2014, 4(1), 181-201; doi:10.3390/biom4010181
Received: 9 January 2014; in revised form: 7 February 2014 / Accepted: 9 February 2014 / Published: 10 February 2014
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p. 56-75
by , , ,  and
Biomolecules 2014, 4(1), 56-75; doi:10.3390/biom4010056
Received: 1 December 2013; in revised form: 17 December 2013 / Accepted: 27 December 2013 / Published: 7 January 2014
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p. 20-55
by ,  and
Biomolecules 2014, 4(1), 20-55; doi:10.3390/biom4010020
Received: 4 November 2013; in revised form: 13 December 2013 / Accepted: 17 December 2013 / Published: 27 December 2013
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p. 1-19
by , , ,  and
Biomolecules 2014, 4(1), 1-19; doi:10.3390/biom4010001
Received: 6 November 2013; in revised form: 10 December 2013 / Accepted: 20 December 2013 / Published: 24 December 2013
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(This article belongs to the Special Issue Protein Folding and Misfolding)
p. 1030-1052
by ,  and
Biomolecules 2013, 3(4), 1030-1052; doi:10.3390/biom3041030
Received: 21 October 2013; in revised form: 6 December 2013 / Accepted: 13 December 2013 / Published: 18 December 2013
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p. 997-1029
by
Biomolecules 2013, 3(4), 997-1029; doi:10.3390/biom3040997
Received: 4 November 2013; in revised form: 26 November 2013 / Accepted: 27 November 2013 / Published: 10 December 2013
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p. 986-996
by , , ,  and
Biomolecules 2013, 3(4), 986-996; doi:10.3390/biom3040986
Received: 29 October 2013; in revised form: 27 November 2013 / Accepted: 28 November 2013 / Published: 6 December 2013
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p. 967-985
by , ,  and
Biomolecules 2013, 3(4), 967-985; doi:10.3390/biom3040967
Received: 9 September 2013; in revised form: 28 October 2013 / Accepted: 29 October 2013 / Published: 18 November 2013
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p. 848-869
by ,  and
Biomolecules 2013, 3(4), 848-869; doi:10.3390/biom3040848
Received: 7 August 2013; in revised form: 27 September 2013 / Accepted: 12 October 2013 / Published: 21 October 2013
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p. 703-732
by , ,  and
Biomolecules 2013, 3(3), 703-732; doi:10.3390/biom3030703
Received: 13 September 2013; in revised form: 21 September 2013 / Accepted: 23 September 2013 / Published: 24 September 2013
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Review
Title:
Protein Stability, Folding and Misfolding in Human PGK1 Deficiency
Authors:
Giovanna Valentini, Maristella Maggi and Angel L. Pey *
Affiliation: Department of Physical Chemistry, Faculty of Sciences, University of Granada, Granada 18071, Spain; * E-Mail: angelpey@ugr.es
Abstract:
Conformational diseases are often caused by mutations altering protein folding and stability in vivo. We review here our recent works on the effects of mutations on the thermodynamics and kinetics of folding and misfolding in the human phosphoglycerate kinase 1 (hPGK1). Expression analyses and in vitro biophysical studies indicate that disease causing mutations enhance protein aggregation propensity. We found a strong correlation between protein aggregation propensity, thermodynamic stability, cooperativity and dynamics. Comparison of folding and unfolding properties with previous reports in PGKs from other species suggests that hPGK1 is very sensitive to mutations leading to enhance protein aggregation through changes in protein folding cooperativity and the structure of the relevant denaturation transition state. Overall, we provide a mechanistic framework of protein misfolding of hPGK1 which is insightful to develop new therapeutic strategies aimed to target native state stability and foldability in hPGK1 deficient patients.

Type of Paper: Article
Title:
Variations in the Structure and Protein Folding Activity of Nine Endoplasmic Reticulum-Localized Protein Disulfide Isomerases in Arabidopsis
Authors:
Christen Y.L. Yuen, Kristie O. Matusumoto and David A. Christopher
Affiliation: Molecular Biosciences & Bioengineering, University of Hawaii, 1955 East-West Rd. AGsciences 218, Honolulu, HI 96822, USA; * E-Mail: dchr@hawaii.edu
Abstract:
Protein disulfide isomerases (PDIs) catalyze the formation, breakage, and rearrangement of disulfide bonds to properly fold nascent polypeptides within the endoplasmic reticulum (ER). Classical animal and yeast PDIs possess two catalytic thioredoxin-like domains (a, a’) and two non-catalytic domains (b, b’), in the order a-b-b’-a’. The model plant, Arabidopsis thaliana, encodes 12 PDI-like proteins, six of which possess the classical PDI domain arrangement (AtPDI1 through AtPDI6). Three additional AtPDIs (AtPDI9, AtPDI10, AtPDI11) possess two thioredoxin domains, but without intervening b-b’ domains. C-terminal green fluorescent protein (GFP) fusions to each of the nine dual-thioredoxin PDI homologs localized predominantly to the ER lumen when transiently expressed in protoplasts. Additionally, expression of AtPDI9:GFP-KDEL or AtPDI10:GFP-KDDL induced the formation of ER bodies. AtPDI9, AtPDI10, and AtPDI11 mediated the oxidative folding of alkaline phosphatase when heterologously expressed in the Escherichia coli protein folding mutant, dsbA. However, only three classical AtPDIs (AtPDI2, AtPDI5, AtPDI6) functionally complemented dsbA-. Interestingly, chemical inducers of the ER unfolded protein response were previously shown to upregulate most of AtPDIs that complemented dsbA-. The results indicate that Arabidopsis PDIs differ in their localization and protein folding activities to fulfill distinct molecular functions in the ER.

Type of Paper: Review
Title:
Refolding Techniques of Active Recombinant Proteins from Inclusion Bodies
Authors:
Hiroshi Yamaguchi and Masaya Miyazaki *
Affiliations
: Department of Molecular and Material Sciences, Interdisciplinary Graduate School of Engineering Sciences, Kyushu University, 6-1, Kasuga-Kouen, Kasuga, Japan; * E-Mail: m.miyazaki@aist.go.jp
Abstract:
Biologically active recombinant proteins are useful for studies of biological functions of genes and for the development of therapeutic drugs and biomaterials in the industries. Protein refolding is an important process to obtain active recombinant proteins from inclusion bodies that contain relatively pure and intact recombinant proteins. However, the conventional refolding method of dialysis or dilution is a time consuming procedure and often, recovering yields of active proteins are low. Recently, several approaches have been reported to refold these aggregated proteins into a biologically active form. In this review, we will focus on a protein refolding methods using chemical additives, solid phase-based techniques and laminar flow in microfluidic chips for efficient recovery of active proteins from inclusion bodies. Each technique (method) will be introduced by its principle, application, strong and weak points.

Type of Paper: Article
Title:
Two Peaks of Heat Capacity in a Short Peptide Chignolin Solution Related to Phase Transitions by an Enhanced Conformational Sampling Simulation
Author
s: Koji Umezawa 1,*, Mitsunori Takano, 1 and Junichi Higo 2
Affiliations
:
1
Graduate school of advanced science and engineering, Waseda University, Okubo 3-4-1, Shinjuku-Ku, Tokyo 169-8555, Japan;
2 Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan; * E-Mails: k.umezawa@aoni.waseda.jp (K.U.); mtkn@waseda.jp (M.T.); higo@protein.osaka-u.ac.jp (J.H.)
Abstract:
Phase-transition-like conformational change of a protein is a major topic in protein folding study. It has been reported experimentally that a 10-residue -hairpin peptide, chignolin, exhibits a transition at room temperature (312 K). We have performed a multicanonical molecular dynamics (McMD) simulation, one of enhanced conformational sampling methods, where the peptide was expressed by an all-atom model and surrounded by an explicit solvent. The McMD simulation has provided temperature dependence of thermodynamic quantities in a wide temperature range [140-700 K]. Interestingly, the heat capacity has exhibited two peaks at 310 K and 180 K. The 310-K peak was related to the folding-unfolding transition, below which chignolin adopted native-like structures. Thus, this transition likely corresponds to the experimentally observed one. The 180-K transition, which is incapable of being detected by an experiment, corresponded to an ordering-disordering transition of the solution structure surrounding chignolin. Free-energy landscapes of the system, derived from the McMD trajectory data, have characterized the phase transitions. In general, to reproduce a phase transition of a biological system by simulation is a difficult task even for a small peptide when it is represented by all-atom model immersed in an explicit solvent. The current study has shown that McMD can reproduce not only native-like structure but also its free-energy landscapes.

Type of Paper: Article
Title: Conformational Biases and Local Order in the Unfolded State: Mediation by Solvent and Nearest Neighbor Interactions
Authors: Siobhan Toal * and Reinhard Schweitzer-Stenner
Affiliation: Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA; E-Mails: siobhan.toal@gmail.com (S.T.); RSchweitzer-Stenner@drexel.edu (R.S.S.)
Abstract: The discovery of Intrinsically Disordered Proteins, which contain significant levels of disorder yet undergo complex biologically functions, as well as unwanted aggregation, has motivated numerous experimental and theoretical studies aimed at describing residue level conformational ensembles. It is now well established that amino acids residues display unique conformational preferences in the unfolded state. To fully understand residue level order/disorder, however, one has to address the physical basis underlying residue-level conformational bias. Here, we review the experimental and theoretical evidence for unique conformational propensities in the unfolded state as well as how these are modulated by peptide solvent interactions, co-solvation, and so called nearest neighbor interactions. We show that the thermodynamics governing the free energy landscape of intrinsic propensities displays enthalpy-entropy entropy compensation when solvated by water and that local order in the form of stable turns can be achieved in aqueous solution. We discuss the implications for local order/disorder in the unfolded state as well as for protein folding.

Type of Paper: Article
Title:
GroEL Chaperonin Reassembly: the Effect of the Protein Ligands and Solvent Composition
Author
: Gennady V. Semisotnov
Affiliation:
Institute of Protein Research, Russian Academy of Sciences, 142290, Russian Federation, Pushchino, Moscow Region, Institutskaya street, 4, Russia; E-Mail: siobhan nina@vega.protres.ru (G.V.S.)
Abstract:
GroEL chaperonin is complex oligomeric heat shock protein (Hsp60) assisting the correct folding and assembly of other proteins in the cell. One from intriguing questions is how GroEL folds itself. According to literary data GroEL reassembly is dependent on chaperonin’ ligands and solvent composition. Here we demonstrate the dependence of GroEL reassembly efficiency on concentration of the essential factors (Mg2+ ions, ADP, ATP, GroES, ammonium sulfate, NaCl and glycerol). Besides, GroEL oligomerization kinetics at various conditions were registrated by light scattering technique. These kinetics are two-exponential hinting on the accumulation of some oligomeric intermediate. This intermediate is resolved by nondenaturing electrophoresis of GroEL monomers in the presence of Mg-ATP and, probably, play a key role in the formation of GroEL tetradecameric particle. The role of co-chaperonin GroES in GroEL assembly is also discussed.

Type of Paper: Review
Title: Misfolding of Amyloidogenic Proteins and Their Interactions with Membranes
Authors: Annalisa Relini 1, Nadia Marano 1,2 and Alessandra Gliozzi 1
Affiliations:
1
Department of Physics, University of Genoa, Genoa, Italy
2 Department of Chemistry, Saint Lawrence University, Canton, NY, USA; E-Mail: gliozzi@fisica.unige.it (A.G.)
Abstract: We discuss amyloidogenic proteins, their misfolding, resulting structures, and interactions with membranes, which lead to membrane damage and subsequent cell death. Many of these proteins are implicated in serious illnesses such as Alzheimer’s disease and Parkinson’s disease. Because oligomeric aggregates are widely thought to be the toxic species, we focus on the structure of these aggregates and their interactions with model membranes. Study of interactions of amlyoidogenic proteins with model and natural membranes has led to a realization of the role of the lipid bilayer in protein misfolding and aggregation, and to the development of several models for membrane permeabilization by the resulting amyloid aggregates. We discuss several of these models: formation of structured pores by misfolded amyloidogenic proteins, extraction of lipids by these proteins, interactions of these proteins with receptors in biological membranes, and membrane destabilization perhaps analogous to that caused by antimicrobial peptides.

Type of Paper: Review
Title: Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol
Author: Ken Teter
Affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL  32826, USA; E-Mail: kteter@mail.ucf.edu
Abstract: AB toxins enter a host cell by receptor-mediated endocytosis.  The catalytic A chain then crosses the endosome or endoplasmic reticulum (ER) membrane to reach its cytosolic target.  Dissociation of the A chain from the cell-binding B chain occurs before or during translocation to the cytosol, and only the A chain enters the cytosol.  In some cases, AB subunit dissociation is facilitated by the unique physiology and function of the ER. The A chains of these ER-translocating toxins are stable within the architecture of the AB holotoxin, but toxin disassembly results in spontaneous or assisted unfolding of the isolated A chain.  This unfolding event places the A chain in a translocation-competent conformation that promotes its ER-to-cytosol export through the quality control mechanism of ER-associated degradation.  A lack of lysine residues for ubiquitin conjugation protects the exported A chain from degradation by the ubiquitin-proteasome system, and an interaction with host factors allows the cytosolic toxin to regain a folded, active state.  The intrinsic instability of the toxin A chain thus influences multiple steps of the intoxication process.  This review will focus on the host-toxin interactions involved with A chain unfolding in the ER and A chain refolding in the cytosol.

Type of Paper: Article
Title:
Folding Proteins by Neural Network Pairwise Interaction Fields and Iterative Decoy Set Construction
Author:
Gianluca Pollastri
Affiliation: Complex and Adaptive Systems Lab, School of Computer Science and Informatics, UCD Dublin, Belfield, Dublin 4, Ireland; E-Mail: gianluca.pollastri@ucd.ie
Abstract:
Predicting the fold of a protein from its amino acid sequence is one of the grand problems in computational biology. While there has been progress towards a solution, especially when a protein can be modelled based on one or more known structures (templates), in the absence of templates even the best predictions are generally much less reliable. In this paper we present a new approach to protein folding in the absence of templates. This approach relies on a reconstruction procedure guided by a potential function implemented as a class of Artificial Neural Networks we have designed: Neural Network Pairwise Interaction Fields (NNPIF). This potential function takes into account contextual information for each residue, and is trained to identify native-like conformations from non native-like ones by using large sets of decoys as a training set. The training set is iteratively expanded during successive folding simulations. As NNPIF are fast, thousands of models can be evaluated in a short amount of time and clustering techniques can be adopted for model selection. Although the results we present here are preliminary, we consider them to be promising, with predictions being generated at state of the art levels in some of the cases.

Type of Paper: Article
Title:
Kinetics and Thermodynamics of Membrane Protein Folding
Authors:
Ernesto A. Roman and F. Luis González Flecha
Affiliation:
Laboratorio de Biofísica Molecular, Instituto de Química y Fisicoquímica Biológicas, Universidad de Buenos Aires-CONICET, Argentina; E-Mail: lgf@qb.ffyb.uba.ar (L.G.F.)
Abstract:
After Anfinsen work demonstrated that protein folding could be efficiently performed in vitro, characterization of protein unfolding and refolding has been extensively attempted. Over the past 40 years a lot of thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparison, advances in the membrane protein folding field has been slower. Although membrane proteins constitute about a third of the proteins encoded in known genomes, obtaining essential data on membrane protein stability has been impaired due to experimental limitations. Despite possible, folding membrane proteins in vitro hitherto lack of systematic experimental strategies. Common denaturing agents such as chaotropes usually do not work on membrane proteins, and ionic detergents have been successful only in few cases. Refolding a membrane protein seems to be a craftsman job; while transmembrane β-barrel proteins easily refold, folding α-helical membrane proteins is challenging. In multidomain membrane proteins additional complexities emerge, being data interpretation one of the most critical. In this review, we focus on membrane proteins that have been reversibly refolded allowing both thermodynamic and kinetic analysis. We will describe some of the better studied systems and discuss the obtained information, comparing it with current understanding of globular protein folding.

Type of Paper: Article
Title:
A Novel Branch-and-Bound Algorithm for the Protein Folding Problem in the 3D-HP Model
Author:
Hsin-Hung Chou 1,*, Chao-Wen Huang 2, Yueh-Chen Lin 2 and Sun-Yuan Hsieh 2
Affiliations:
1 Department of Information Management, Chang Jung Christian University, No.1, Changda Road, Gueiren District, Tainan City 71101, Taiwan; E-Mail: chouhh@mail.cjcu.edu.tw (H.-H. C.); 2 Department of Computer Science and Information Engineering, Institute of Medical Informatics, Institute of Manufacturing Information and Systems, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan; E-Mails: huang_c_w@hotmail.com (C.-W. H.); hsiehsy@mail.ncku.edu.tw (S.-Y. H.); hyde@iis.sinica.edu.tw (Y.-C. Lin.)
Abstract:
The protein folding problem is a fundamental issue in bioinformatics and biochemical physics. The object of the problem is to make a structure prediction of a protein from its amino acid sequence. The problem is a well-known NP-hard problem even under the simplified lattice model. Therefore, the existing algorithms for solving the problem can only predict a near-optimal structure from the benchmark sequences. In this paper, we propose a novel algorithm based on the branch-and-bound strategy to solve the protein folding problem in the 3D HP model. The experiment shows that our algorithm outperforms the other existing approaches.
Keywords:
Bioinformatics; Branch-and-bound algorithm; Computational biology; HP model; Protein folding problem

Type of Paper: Review
Title: Structure and Function of the LmbE-like Superfamily
Author: Marcy Hernick
Affiliation: Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, Oakwood, VA 24631, USA; E-Mail: MHernick@acp.edu (M.H.)
Abstract: The LmbE-like superfamily is comprised of a series of enzymes that use a single catalytic metal ion to catalyze the hydrolysis various substrates. These substrates are often key metabolites for eukaryotes and prokaryotes, which makes the LmbE-like enzymes important targets for drug development. Herein we review the structure and function of the LmbE-like proteins identified to date. While this is the newest superfamily of metallohydrolases, a growing number of functionally interesting proteins from this superfamily have been characterized. Available crystal structures of LmbE-like proteins reveal a Rossman fold similar to lactate dehydrogenase, which represented a novel fold for (zinc) metallohydrolases at the time the initial structure was solved. There is remarkable structural diversity amongst the substrates for the LmbE-like enzymes that translates into functional diversity for this enzyme superfamily. The majority of enzymes identified to date are metal-dependent deacetylases that catalyze the hydrolysis of a N-acetylglucosamine moiety on substrate using a combination of amino acid side chains and a single bound metal ion, most commonly zinc or iron. Additionally, studies indicate that protein dynamics play important roles in regulating access to the active site and facilitating catalysis for at least two members of this protein superfamily.

Type of Paper: Review
Title:
Transient non-native helix formation during folding of b-lactoglobulin
Author:
Masamichi Ikeguchi
Affiliation:
Department of Bioinformatics, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan; E-Mail: ikeguchi@soka.ac.jp (M.I.)
Abstract:
For ideal proteins, only native interactions are stabilized step-by-step in a smooth funnel-like energy landscape. For real proteins, however, transient formation of non-native structures are frequently observed. In this review, transient formation of non-native structure, especially as a prominent example, the non-native helix formation during the folding of b-lactoglobulin is described. Although b-lactoglobulin is a predominantly b-sheet protein, it has been shown to form non-native helices during an early stage of folding. The location of non-native helices, their stabilization mechanism, and their role in the folding reaction will be discussed.

Last update: 10 February 2014

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