scholarly journals Folding processes of the B domain of protein A to the native state observed in all-atom ab initio folding simulations

2008 ◽  
Vol 128 (23) ◽  
pp. 235105 ◽  
Author(s):  
Hongxing Lei ◽  
Chun Wu ◽  
Zhi-Xiang Wang ◽  
Yaoqi Zhou ◽  
Yong Duan
Keyword(s):  
Ab Initio ◽  
Protein A ◽  
Native State ◽  
Folding Simulations

STUDY OF FOLDING BEHAVIORS OF A SIX-HELIX PROTEIN BY ab initio MOLECULAR DYNAMICS FOLDING SIMULATIONS OF UNRES

2009 ◽  
Vol 20 (03) ◽  
pp. 373-382 ◽  
Author(s):  
YI HE ◽  
RUI ZHOU ◽  
YI XIAO
Keyword(s):  
Molecular Dynamics ◽  
Ab Initio ◽  
Tertiary Structure ◽  
Secondary Structures ◽  
Protein Domain ◽  
Ab Initio Molecular Dynamics ◽  
Native State ◽  
Folding Process ◽  
Hydrophobic Collapse ◽  
Folding Simulations

In this paper, we employ united-residue (UNRES) approach to study folding processes of a six-helix protein domain (the C-terminal domain of Ku86 protein, PDB ID: 1Q2Z). We simulated forty-eight 110-ns independent molecular dynamics trajectories with UNRES starting from extended conformations for this protein. The protein domain successfully folds into its native state and the results show that its folding process is relatively simple: first, the secondary structures form very fast with the hydrophobic collapse, then helix pairs form, and finally these pairs assemble into the tertiary structure. We also find the first-half (the first three helices) and last-half (the last three helices) parts of this protein domain can fold into their native conformations independently and this suggests that this protein may be evolved from smaller polypeptide or protein.

scholarly journals Efficient Refolding of Aggregation-prone Citrate Synthase by Polyol Osmolytes

2005 ◽  
Vol 280 (16) ◽  
pp. 15553-15560 ◽  
Author(s):  
Rajesh Mishra ◽  
Robert Seckler ◽  
Rajiv Bhat
Keyword(s):  
Small Molecules ◽  
Molecular Chaperones ◽  
Rational Design ◽  
Protein Production ◽  
Citrate Synthase ◽  
Protein A ◽  
Complete Recovery ◽  
Hydroxyl Groups ◽  
Native State

Efficient refolding of proteins and prevention of their aggregation during folding are of vital importance in recombinant protein production and in finding cures for several diseases. We have used citrate synthase (CS) as a model to understand the mechanism of aggregation during refolding and its prevention using several known structure-stabilizing cosolvent additives of the polyol series. Interestingly, no parallel correlation between the folding effect and the general stabilizing effect exerted by polyols was observed. Although increasing concentrations of polyols increased protein stability in general, the refolding yields for CS decreased at higher polyol concentrations, with erythritol reducing the folding yields at all concentrations tested. Among the various polyols used, glycerol was the most effective in enhancing the CS refolding yield, and a complete recovery of enzymatic activity was obtained at 7mglycerol and 10 μg/ml protein, a result superior to the action of the molecular chaperones GroEL and GroESin vitro. A good correlation between the refolding yields and the suppression of protein aggregation by glycerol was observed, with no aggregation detected at 7m. The polyols prevented the aggregation of CS depending on the number of hydroxyl groups in them. Stopped-flow fluorescence kinetics experiments suggested that polyols, including glycerol, act very early in the refolding process, as no fast and slow phases were detectable. The results conclusively demonstrate that both the thermodynamic and kinetic aspects are critical in the folding process and that all structure-stabilizing molecules need not always help in productive folding to the native state. These findings are important for the rational design of small molecules for efficient refolding of various aggregation-prone proteins of commercial and medical relevance.

scholarly journals Optimized folding simulations of protein A

2007 ◽  
Vol 24 (3) ◽  
pp. 311-316 ◽  
Author(s):  
S. Trebst ◽  
U. H. E. Hansmann
Keyword(s):  
Protein A ◽  
Folding Simulations

scholarly journals Fueling ab initio folding with marine metagenomics enables structure and function predictions of new protein families

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Wang ◽  
Qiang Shi ◽  
Pengshuo Yang ◽  
Chengxin Zhang ◽  
S. M. Mortuza ◽  
...  
Keyword(s):  
Protein Structure ◽  
Ab Initio ◽  
Structure Prediction ◽  
Primary Energy ◽  
Structure And Function ◽  
Protein Structure And Function ◽  
New Protein Families ◽  
Highly Correlated ◽  
Folding Simulations ◽  
And Function

Abstract Introduction The ocean microbiome represents one of the largest microbiomes and produces nearly half of the primary energy on the planet through photosynthesis or chemosynthesis. Using recent advances in marine genomics, we explore new applications of oceanic metagenomes for protein structure and function prediction. Results By processing 1.3 TB of high-quality reads from the Tara Oceans data, we obtain 97 million non-redundant genes. Of the 5721 Pfam families that lack experimental structures, 2801 have at least one member associated with the oceanic metagenomics dataset. We apply C-QUARK, a deep-learning contact-guided ab initio structure prediction pipeline, to model 27 families, where 20 are predicted to have a reliable fold with estimated template modeling score (TM-score) at least 0.5. Detailed analyses reveal that the abundance of microbial genera in the ocean is highly correlated to the frequency of occurrence in the modeled Pfam families, suggesting the significant role of the Tara Oceans genomes in the contact-map prediction and subsequent ab initio folding simulations. Of interesting note, PF15461, which has a majority of members coming from ocean-related bacteria, is identified as an important photosynthetic protein by structure-based function annotations. The pipeline is extended to a set of 417 Pfam families, built on the combination of Tara with other metagenomics datasets, which results in 235 families with an estimated TM-score over 0.5. Conclusions These results demonstrate a new avenue to improve the capacity of protein structure and function modeling through marine metagenomics, especially for difficult proteins with few homologous sequences.

A Symmetry-Free Subspace for Ab initio Protein Folding Simulations

2008 ◽  
pp. 128-139 ◽  
Author(s):  
Xiangchao Gan ◽  
Leonidas Kapsokalivas ◽  
Andreas A. Albrecht ◽  
Kathleen Steinhöfel
Keyword(s):  
Protein Folding ◽  
Ab Initio ◽  
Folding Simulations

Ab initio protein folding simulations using atomic burials as informational intermediates between sequence and structure

2013 ◽  
Vol 82 (7) ◽  
pp. 1186-1199 ◽  
Author(s):  
Marx Gomes van der Linden ◽  
Diogo César Ferreira ◽  
Leandro Cristante de Oliveira ◽  
José N. Onuchic ◽  
Antônio F. Pereira de Araújo
Keyword(s):  
Protein Folding ◽  
Ab Initio ◽  
Folding Simulations
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