scholarly journals Distance-based Reconstruction of Protein Quaternary Structures from Inter-Chain Contacts

2021 ◽  
Author(s):  
Elham Soltanikazemi ◽  
Farhan Quadir ◽  
Raj Roy ◽  
Jianlin Cheng
Keyword(s):  
Quaternary Structure ◽  
Structural Models ◽  
Simulation Method ◽  
Contact Density ◽  
High Quality ◽  
Contact Prediction ◽  
Residue Contact ◽  
Protein Dimers ◽  
Distance Restraints ◽  
Quaternary Structures

Predicting the quaternary structure of protein complex is an important problem. Inter-chain residue-residue contact prediction can provide useful information to guide the ab initio reconstruction of quaternary structures. However, few methods have been developed to build quaternary structures from predicted inter-chain contacts. Here, we introduce a gradient descent optimization algorithm (GD) to build quaternary structures of protein dimers utilizing inter-chain contacts as distance restraints. We evaluate GD on several datasets of homodimers and heterodimers using true or predicted contacts. GD consistently performs better than a simulated annealing method and a Markov Chain Monte Carlo simulation method. Using true inter-chain contacts as input, GD can reconstruct high-quality structural models for homodimers and heterodimers with average TM-score ranging from 0.92 to 0.99 and average interface root mean square distance (I-RMSD) from 0.72 Å to 1.64 Å. On a dataset of 115 homodimers, using predicted inter-chain contacts as input, the average TM-score of the structural models built by GD is 0.76. For 46% of the homodimers, high-quality structural models with TM-score >= 0.9 are reconstructed from predicted contacts. There is a strong correlation between the quality of the reconstructed models and the precision and recall of predicted contacts. If the precision or recall of predicted contacts is >20%, GD can reconstruct good models for most homodimers, indicating only a moderate precision or recall of inter-chain contact prediction is needed to build good structural models for most homodimers. Moreover, the accuracy of reconstructed models positively correlates with the contact density in dimers.

scholarly journals Distance-based Reconstruction of Protein Quaternary Structures from Inter-Chain Contacts

2021 ◽  
Author(s):  
Elham Soltanikazemi ◽  
Farhan Quadir ◽  
Raj Shekhor Roy ◽  
Jianlin Cheng
Keyword(s):  
Quaternary Structure ◽  
Protein Complexes ◽  
Structural Models ◽  
Simulation Method ◽  
Contact Density ◽  
High Quality ◽  
Contact Prediction ◽  
Protein Dimers ◽  
Probability Threshold ◽  
Quaternary Structures

Predicting the quaternary structure of a protein complex is an important and challenging problem. Inter-chain residue-residue contact prediction can provide useful information to guide the ab initio reconstruction of quaternary structures of protein complexes. However, few methods have been developed to build quaternary structures from predicted inter-chain contacts. Here, we introduce a new gradient descent optimization algorithm (GD) to build quaternary structures of protein dimers utilizing inter-chain contacts as distance restraints. We evaluate GD on several datasets of homodimers and heterodimers using true or predicted contacts. GD consistently performs better than a simulated annealing method and a Markov Chain Monte Carlo simulation method. Using true inter-chain contacts as input, GD can reconstruct high-quality structural models for homodimers and heterodimers with average TM-score ranging from 0.92 to 0.99 and average interface root mean square distance (I-RMSD) from 0.72 Å to 1.64 Å. On a dataset of 115 homodimers, using predicted inter-chain contacts as input, the average TM-score of the structural models built by GD is 0.76. For 46% of the homodimers, high-quality structural models with TM-score >= 0.9 are reconstructed from predicted contacts. There is a strong correlation between the quality of the reconstructed models and the precision and recall of predicted contacts. If the precision or recall of predicted contacts is >20%, GD can reconstruct good models for most homodimers, indicating only a moderate precision or recall of inter-chain contact prediction is needed to build good structural models for most homodimers. Moreover, the accuracy of reconstructed models positively correlates with the contact density in dimers and depends on the initial model and the probability threshold of selecting predicted contacts for the distance-based structure optimization.

scholarly journals DR-SIP: Protocols for Higher Order Structure Modeling with Distance Restraints- and Cyclic Symmetry-Imposed Packing

2018 ◽  
Author(s):  
Justin Chan ◽  
Jinhao Zou ◽  
Chi-Hong Chang Chien ◽  
Rong-Long Pan ◽  
Lee-Wei Yang
Keyword(s):  
Structure Determination ◽  
Quaternary Structure ◽  
Transmembrane Proteins ◽  
Computational Prediction ◽  
Higher Order ◽  
The Other ◽  
Order Structure ◽  
Cyclic Symmetry ◽  
Distance Restraints ◽  
Quaternary Structures

Motivation: Quaternary structure determination for proteins is difficult especially for transmembrane proteins. Even if the monomeric constituents of complexes have been experimentally resolved, computational prediction of quaternary structures is a challenging task particularly for higher order complexes. It is essential to have a reliable computational protocol to predict quaternary structures of both transmembrane and soluble proteins leveraging experimentally determined distance restraints and/or cyclic symmetry (Cn symmetry) found in most homo-oligomeric transmembrane proteins. Results: We survey 115 X-ray crystallographically solved structures of homo-oligomeric transmembrane proteins (HoTPs) to discover that 90% of them are Cn symmetric. Given the prevalence of Cn symmetric HoTPs and the benefits of incorporating geometry restraints in aiding quaternary structure determination, we introduce two new filters, the distance-restraints (DR) filter and the Symmetry-Imposed Packing (SIP) filter which takes advantage of the statistically derived tilt angle cutoff and the Cn symmetry of HoTPs without prior knowledge of the number ("n") of monomers. Using only the geometrical filter, SIP, near-native poses of the 115 HoTPs can be correctly identified in the top-5 for 52% of all cases, or 49% among the HoTPs having an n>2 (~60% of the dataset), while ZDOCK alone returns 41% and 24%, respectively. Applying only SIP to three HoTPs with distance restraints, the near-native poses for two HoTPs are ranked 1st and the other 7th among 54,000 possible decoys. With both filters, the two remain 1st while the other improved to 2nd. While a soluble system with distance restraints is recovered at the 1st-ranked pose by applying only DR.

scholarly journals Evaluation of residue-residue contact prediction methods: From retrospective to prospective

2021 ◽  
Vol 17 (5) ◽  
pp. e1009027
Author(s):  
Huiling Zhang ◽  
Zhendong Bei ◽  
Wenhui Xi ◽  
Min Hao ◽  
Zhen Ju ◽  
...  
Keyword(s):  
Hydrophobic Interactions ◽  
Great Success ◽  
Sequence Alignments ◽  
Contact Density ◽  
Data Set ◽  
Contact Prediction ◽  
Intrinsically Disordered ◽  
Residue Contact ◽  
Wide Range ◽  
Training Sets

Sequence-based residue contact prediction plays a crucial role in protein structure reconstruction. In recent years, the combination of evolutionary coupling analysis (ECA) and deep learning (DL) techniques has made tremendous progress for residue contact prediction, thus a comprehensive assessment of current methods based on a large-scale benchmark data set is very needed. In this study, we evaluate 18 contact predictors on 610 non-redundant proteins and 32 CASP13 targets according to a wide range of perspectives. The results show that different methods have different application scenarios: (1) DL methods based on multi-categories of inputs and large training sets are the best choices for low-contact-density proteins such as the intrinsically disordered ones and proteins with shallow multi-sequence alignments (MSAs). (2) With at least 5L (L is sequence length) effective sequences in the MSA, all the methods show the best performance, and methods that rely only on MSA as input can reach comparable achievements as methods that adopt multi-source inputs. (3) For top L/5 and L/2 predictions, DL methods can predict more hydrophobic interactions while ECA methods predict more salt bridges and disulfide bonds. (4) ECA methods can detect more secondary structure interactions, while DL methods can accurately excavate more contact patterns and prune isolated false positives. In general, multi-input DL methods with large training sets dominate current approaches with the best overall performance. Despite the great success of current DL methods must be stated the fact that there is still much room left for further improvement: (1) With shallow MSAs, the performance will be greatly affected. (2) Current methods show lower precisions for inter-domain compared with intra-domain contact predictions, as well as very high imbalances in precisions for intra-domains. (3) Strong prediction similarities between DL methods indicating more feature types and diversified models need to be developed. (4) The runtime of most methods can be further optimized.

scholarly journals Macromolecular Nanocrystal Structural Analysis with Electron and X-Rays: A Comparative Review

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3490
Author(s):  
Krishna P. Khakurel ◽  
Borislav Angelov ◽  
Jakob Andreasson
Keyword(s):  
Structural Analysis ◽  
Structural Models ◽  
X Rays ◽  
High Quality ◽  
X Ray ◽  
Detection Techniques ◽  
Comparative Review

Crystallography has long been the unrivaled method that can provide the atomistic structural models of macromolecules, using either X-rays or electrons as probes. The methodology has gone through several revolutionary periods, driven by the development of new sources, detectors, and other instrumentation. Novel sources of both X-ray and electrons are constantly emerging. The increase in brightness of these sources, complemented by the advanced detection techniques, has relaxed the traditionally strict need for large, high quality, crystals. Recent reports suggest high-quality diffraction datasets from crystals as small as a few hundreds of nanometers can be routinely obtained. This has resulted in the genesis of a new field of macromolecular nanocrystal crystallography. Here we will make a brief comparative review of this growing field focusing on the use of X-rays and electrons sources.

Nano-Tech Power Cables

2021 ◽  
pp. 39-76
Keyword(s):  
Power Law ◽  
Electrostatic Field ◽  
Partial Discharge ◽  
Dielectric Strength ◽  
Simulation Method ◽  
The Novel ◽  
Power Cables ◽  
Effective Parameters ◽  
Charge Simulation Method ◽  
High Quality

This chapter explores the novel nano-metric present-day materials considering power law Profile PLP for redesigning the electrostatic field circulation in the insulation of power cables assessed for scrutinizing charge simulation method (CSM). Moreover, this chapter presents a deep study for using individual and multiple nanodielectrics in power cables manufacturing. An investigation on dielectric strength and partial discharges in the nanodielectrics of power cables is also presented. Furthermore, it offers a detailed theory and effective parameters of partial discharge in nanodielectrics of power cables. Finally, forecast and recommendations are offered for manufacturers to fabricate high quality commercial nano-tech power cables.

scholarly journals Aβ(M1–40) and Wild-Type Aβ40 Self-Assemble into Oligomers with Distinct Quaternary Structures

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2242 ◽  
Author(s):  
Jacob L. Bouchard ◽  
Taylor C. Davey ◽  
Todd M. Doran
Keyword(s):  
Self Assembly ◽  
Quaternary Structure ◽  
Biological Activities ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Wild Type ◽  
Molecular Weights ◽  
Term Potentiation ◽  
Quaternary Structures

Amyloid-β oligomers (AβOs) self-assemble into polymorphic species with diverse biological activities that are implicated causally to Alzheimer’s disease (AD). Synaptotoxicity of AβO species is dependent on their quaternary structure, however, low-abundance and environmental sensitivity of AβOs in vivo have impeded a thorough assessment of structure–function relationships. We developed a simple biochemical assay to quantify the relative abundance and morphology of cross-linked AβOs. We compared oligomers derived from synthetic Aβ40 (wild-type (WT) Aβ40) and a recombinant source, called Aβ(M1–40). Both peptides assemble into oligomers with common sizes and morphology, however, the predominant quaternary structures of Aβ(M1–40) oligomeric states were more diverse in terms of dispersity and morphology. We identified self-assembly conditions that stabilize high-molecular weight oligomers of Aβ(M1–40) with apparent molecular weights greater than 36 kDa. Given that mixtures of AβOs derived from both peptides have been shown to be potent neurotoxins that disrupt long-term potentiation, we anticipate that the diverse quaternary structures reported for Aβ(M1–40) oligomers using the assays reported here will facilitate research efforts aimed at isolating and identifying common toxic species that contribute to synaptic dysfunction.

scholarly journals The process for the activation of frog epidermis pro-tyrosinase

1982 ◽  
Vol 205 (2) ◽  
pp. 397-404 ◽  
Author(s):  
R Peñafiel ◽  
J D Galindo ◽  
E Pedreño ◽  
J A Lozano
Keyword(s):  
Quaternary Structure ◽  
Polypeptide Chain ◽  
Rana Esculenta ◽  
Single Type ◽  
Low Molecular Weight ◽  
Activation Process ◽  
Proteolytic Activation ◽  
Molecular Weights ◽  
Quaternary Structures

1. Purified pro-tyrosinase from epidermis of the frog Rana esculenta ridibunda can be activated in vitro by several proteinases (trypsin, alpha-chymotrypsin, Pronase) and by light. 2. Both pro-tyrosinase and tyrosinase are composed of a single type of subunit having pI 7.2 and approximate molecular weights 68000 and 62000 respectively. A peptide of low molecular weight is released as a consequence of the proteolytic activation. Pro-tyrosinase and tyrosinase have different quaternary structures, the proenzyme being a dimer of Mr approx. 115000 and the enzyme a tetramer of Mr approx. 210 000. 3. The activation process was affected by several agents (L-3,4-dihydroxyphenylalanine, urea, formamide) that prevented, partially or totally, the activation of pro-tyrosinase. 4. The activation of pro-tyrosinase seems to be the result of a cleavage of the polypeptide chain that determines changes in tertiary or quaternary structure.

scholarly journals Forecasting residue–residue contact prediction accuracy

2017 ◽  
Vol 33 (21) ◽  
pp. 3405-3414 ◽  
Author(s):  
P P Wozniak ◽  
B M Konopka ◽  
J Xu ◽  
G Vriend ◽  
M Kotulska
Keyword(s):  
Prediction Accuracy ◽  
Contact Prediction ◽  
Residue Contact
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