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 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 Quantum Information in the Protein Codes, $3$-manifolds and the Kummer Surface

2021 ◽  
Author(s):  
Michel Planat ◽  
Raymond Aschheim ◽  
Marcelo M. Amaral ◽  
Fang Fang ◽  
Klee Irwin
Keyword(s):  
Quaternary Structure ◽  
Protein Complexes ◽  
Dimensional Space ◽  
Linear Chain ◽  
Secondary Structures ◽  
Kummer Surface ◽  
Alpha Helices ◽  
Multiple Structures ◽  
Quaternary Structures ◽  
Mere Existence

Every protein consists of a linear sequence over an alphabet of $20$ letters/amino acids. The sequence unfolds in the $3$-dimensional space through secondary (local foldings), tertiary (bonds) and quaternary (disjoint multiple) structures. The mere existence of the genetic code for the $20$ letters of the linear chain could be predicted with the (informationally complete) irreducible characters of the finite group $G_n:=\mathbb{Z}_n \rtimes 2O$ (with $n=5$ or $7$ and $2O$ the binary octahedral group) in our previous two papers. It turns out that some quaternary structures of protein complexes display $n$-fold symmetries. We propose an approach of secondary structures based on free group theory. Our results are compared to other approaches of predicting secondary structures of proteins in terms of $\alpha$ helices, $\beta$ sheets and coils, or more refined techniques. It is shown that the secondary structure of proteins shows similarities to the structure of some hyperbolic $3$-manifolds. The hyperbolic $3$-manifold of smallest volume --Gieseking manifold--, some other $3$ manifolds and Grothendieck's cartographic group are singled out as tentative models of such secondary structures. For the quaternary structure, there are links to the Kummer surface.

scholarly journals Evolution of interface binding strengths in simplified model of protein quaternary structure

2019 ◽  
Author(s):  
Alexander S. Leonard ◽  
Sebastian E. Ahnert
Keyword(s):  
Self Assembly ◽  
Quaternary Structure ◽  
Protein Complexes ◽  
Lattice Models ◽  
Evolutionary Selection ◽  
Wide Range ◽  
Simple Change ◽  
Quaternary Structures ◽  
Assembly Pathways ◽  
New Framework

AbstractThe self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new framework for the study of protein self-assembly processes and their evolution.

scholarly journals Quantum Information in the Protein Codes, 3-Manifolds and the Kummer Surface

Symmetry ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1146
Author(s):  
Michel Planat ◽  
Raymond Aschheim ◽  
Marcelo M. Amaral ◽  
Fang Fang ◽  
Klee Irwin
Keyword(s):  
Quaternary Structure ◽  
Protein Complexes ◽  
Dimensional Space ◽  
Linear Chain ◽  
Secondary Structures ◽  
Kummer Surface ◽  
Linear Sequence ◽  
Multiple Structures ◽  
Quaternary Structures ◽  
Mere Existence

Every protein consists of a linear sequence over an alphabet of 20 letters/amino acids. The sequence unfolds in the 3-dimensional space through secondary (local foldings), tertiary (bonds) and quaternary (disjoint multiple) structures. The mere existence of the genetic code for the 20 letters of the linear chain could be predicted with the (informationally complete) irreducible characters of the finite group Gn:=Zn⋊2O (with n=5 or 7 and 2O the binary octahedral group) in our previous two papers. It turns out that some quaternary structures of protein complexes display n-fold symmetries. We propose an approach of secondary structures based on free group theory. Our results are compared to other approaches of predicting secondary structures of proteins in terms of α helices, β sheets and coils, or more refined techniques. It is shown that the secondary structure of proteins shows similarities to the structure of some hyperbolic 3-manifolds. The hyperbolic 3-manifold of smallest volume—Gieseking manifold—some other 3 manifolds and the oriented hypercartographic group are singled out as tentative models of such secondary structures. For the quaternary structure, there are links to the Kummer surface.

scholarly journals DeepComplex: A Web Server of Predicting Protein Complex Structures by Deep Learning Inter-chain Contact Prediction and Distance-Based Modelling

2021 ◽  
Vol 8 ◽  
Author(s):  
Farhan Quadir ◽  
Raj S. Roy ◽  
Elham Soltanikazemi ◽  
Jianlin Cheng
Keyword(s):  
Deep Learning ◽  
Protein Function ◽  
Tertiary Structure ◽  
Quaternary Structure ◽  
Protein Complexes ◽  
Function Analysis ◽  
Web Server ◽  
Learning Technology ◽  
Multiple Sequence ◽  
Contact Prediction

Proteins interact to form complexes. Predicting the quaternary structure of protein complexes is useful for protein function analysis, protein engineering, and drug design. However, few user-friendly tools leveraging the latest deep learning technology for inter-chain contact prediction and the distance-based modelling to predict protein quaternary structures are available. To address this gap, we develop DeepComplex, a web server for predicting structures of dimeric protein complexes. It uses deep learning to predict inter-chain contacts in a homodimer or heterodimer. The predicted contacts are then used to construct a quaternary structure of the dimer by the distance-based modelling, which can be interactively viewed and analysed. The web server is freely accessible and requires no registration. It can be easily used by providing a job name and an email address along with the tertiary structure for one chain of a homodimer or two chains of a heterodimer. The output webpage provides the multiple sequence alignment, predicted inter-chain residue-residue contact map, and predicted quaternary structure of the dimer. DeepComplex web server is freely available at http://tulip.rnet.missouri.edu/deepcomplex/web_index.html

scholarly journals Bioinformatics Tools and Benchmarks for Computational Docking and 3D Structure Prediction of RNA-Protein Complexes

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 432 ◽  
Author(s):  
Chandran Nithin ◽  
Pritha Ghosh ◽  
Janusz Bujnicki
Keyword(s):  
Rna Splicing ◽  
Structure Prediction ◽  
Protein Complexes ◽  
3D Structure ◽  
Structural Models ◽  
Computational Prediction ◽  
Computational Docking ◽  
3D Structure Prediction ◽  
Rna Protein Complexes

RNA-protein (RNP) interactions play essential roles in many biological processes, such as regulation of co-transcriptional and post-transcriptional gene expression, RNA splicing, transport, storage and stabilization, as well as protein synthesis. An increasing number of RNP structures would aid in a better understanding of these processes. However, due to the technical difficulties associated with experimental determination of macromolecular structures by high-resolution methods, studies on RNP recognition and complex formation present significant challenges. As an alternative, computational prediction of RNP interactions can be carried out. Structural models obtained by theoretical predictive methods are, in general, less reliable compared to models based on experimental measurements but they can be sufficiently accurate to be used as a basis for to formulating functional hypotheses. In this article, we present an overview of computational methods for 3D structure prediction of RNP complexes. We discuss currently available methods for macromolecular docking and for scoring 3D structural models of RNP complexes in particular. Additionally, we also review benchmarks that have been developed to assess the accuracy of these methods.

scholarly journals Contribution of low-temperature single-molecule techniques to structural issues of pigment–protein complexes from photosynthetic purple bacteria

2018 ◽  
Vol 15 (138) ◽  
pp. 20170680 ◽  
Author(s):  
Alexander Löhner ◽  
Richard Cogdell ◽  
Jürgen Köhler
Keyword(s):  
Low Temperature ◽  
Single Molecule ◽  
Degrees Of Freedom ◽  
Protein Complexes ◽  
Purple Bacteria ◽  
Structural Models ◽  
Spectral Features ◽  
Light Harvesting Complexes ◽  
Pigment Protein Complexes ◽  
Photosynthetic Purple Bacteria

As the electronic energies of the chromophores in a pigment–protein complex are imposed by the geometrical structure of the protein, this allows the spectral information obtained to be compared with predictions derived from structural models. Thereby, the single-molecule approach is particularly suited for the elucidation of specific, distinctive spectral features that are key for a particular model structure, and that would not be observable in ensemble-averaged spectra due to the heterogeneity of the biological objects. In this concise review, we illustrate with the example of the light-harvesting complexes from photosynthetic purple bacteria how results from low-temperature single-molecule spectroscopy can be used to discriminate between different structural models. Thereby the low-temperature approach provides two advantages: (i) owing to the negligible photobleaching, very long observation times become possible, and more importantly, (ii) at cryogenic temperatures, vibrational degrees of freedom are frozen out, leading to sharper spectral features and in turn to better resolved spectra.

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.

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