scholarly journals Analysis of Fluctuation in the Heme-Binding Pocket and Heme Distortion in Hemoglobin and Myoglobin

2021 ◽  
Author(s):  
Hiroko X. Kondo ◽  
Yu Takano
Keyword(s):  
Physical Properties ◽  
Protein Structures ◽  
Oxygen Affinity ◽  
Md Simulations ◽  
Data Bank ◽  
Binding Pocket ◽  
Protein Functions ◽  
Heme Distortion ◽  
The Relationship ◽  
Protein Environment

Heme is located in the active site of proteins and has diverse and important biological functions, such as electron transfer and oxygen transport and/or storage. The distortion of heme porphyrin is considered an important factor for the diverse functions of heme because it correlates with the physical properties of heme, such as oxygen affinity and redox potential. Therefore, clarification of the relationship between heme distortion and the protein environment is crucial in protein science. Here, we analyzed the fluctuation in heme distortion in the protein environment for hemoglobin and myoglobin using molecular dynamics (MD) simulations and quantum mechanical (QM) calculations. We also investigated the protein structures of hemoglobin and myoglobin stored in Protein Data Bank and found that heme is distorted along the doming mode, which correlates with its oxygen affinity, more prominently in the protein environment than in the isolated state, and the magnitude of distortion is different between hemoglobin and myoglobin. This tendency was also observed in the results of MD simulations and QM calculations. These results suggest that heme distortion is affected by its protein environment and fluctuates around its fitted conformation, leading to physical properties that are appropriate for protein functions.

scholarly journals Structure-Based Protein Function Prediction using Graph Convolutional Networks

2019 ◽  
Author(s):  
Vladimir Gligorijevic ◽  
P. Douglas Renfrew ◽  
Tomasz Kosciolek ◽  
Julia Koehler Leman ◽  
Daniel Berenberg ◽  
...  
Keyword(s):  
Protein Function ◽  
Sequence Data ◽  
Protein Function Prediction ◽  
General Structure ◽  
Protein Structures ◽  
Data Bank ◽  
Function Prediction ◽  
Convolutional Network ◽  
Convolutional Networks ◽  
Protein Functions

The large number of available sequences and the diversity of protein functions challenge current experimental and computational approaches to determining and predicting protein function. We present a deep learning Graph Convolutional Network (GCN) for predicting protein functions and concurrently identifying functionally important residues. This model is initially trained using experimentally determined structures from the Protein Data Bank (PDB) but has significant de-noising capability, with only a minor drop in performance observed when structure predictions are used. We take advantage of this denoising property to train the model on > 200,000 protein structures, including many homology-predicted structures, greatly expanding the reach and applications of the method. Our model learns general structure-function relationships by robustly predicting functions of proteins with ≤ 40% sequence identity to the training set. We show that our GCN architecture predicts functions more accurately than Convolutional Neural Networks trained on sequence data alone and previous competing methods. Using class activation mapping, we automatically identify structural regions at the residue-level that lead to each function prediction for every confidently predicted protein, advancing site-specific function prediction. We use our method to annotate PDB and SWISS-MODEL proteins, making several new confident function predictions spanning both fold and function classifications.

scholarly journals Mapping Function from Dynamics: Future Challenges for Network-Based Models of Protein Structures

2021 ◽  
Vol 8 ◽  
Author(s):  
Lorenza Pacini ◽  
Rodrigo Dorantes-Gilardi ◽  
Laurent Vuillon ◽  
Claire Lesieur
Keyword(s):  
Ad Hoc ◽  
Protein Structures ◽  
Protein Composition ◽  
Network Models ◽  
Mapping Function ◽  
Md Simulations ◽  
Data Bank ◽  
Network Measures ◽  
Functional Dynamics ◽  
And Function

Proteins fulfill complex and diverse biological functions through the controlled atomic motions of their structures (functional dynamics). The protein composition is given by its amino-acid sequence, which was assumed to encode the function. However, the discovery of functional sequence variants proved that the functional encoding does not come down to the sequence, otherwise a change in the sequence would mean a change of function. Likewise, the discovery that function is fulfilled by a set of structures and not by a unique structure showed that the functional encoding does not come down to the structure either. That leaves us with the possibility that a set of atomic motions, achievable by different sequences and different structures, encodes a specific function. Thanks to the exponential growth in annual depositions in the Protein Data Bank of protein tridimensional structures at atomic resolutions, network models using the Cartesian coordinates of atoms of a protein structure as input have been used over 20 years to investigate protein features. Combining networks with experimental measures or with Molecular Dynamics (MD) simulations and using typical or ad-hoc network measures is well suited to decipher the link between protein dynamics and function. One perspective is to consider static structures alone as alternatives to address the question and find network measures relevant to dynamics that can be subsequently used for mining and classification of dynamic sequence changes functionally robust, adaptable or faulty. This way the set of dynamics that fulfill a function over a diversity of sequences and structures will be determined.

Protein-ensemble–RNA docking by efficient consideration of protein flexibility through homology models

2019 ◽  
Vol 35 (23) ◽  
pp. 4994-5002 ◽  
Author(s):  
Jiahua He ◽  
Huanyu Tao ◽  
Sheng-You Huang
Keyword(s):  
Complex Structure ◽  
Protein Structures ◽  
Protein Flexibility ◽  
Md Simulations ◽  
Homology Model ◽  
Data Bank ◽  
Supplementary Information ◽  
Scoring Functions ◽  
Ensemble Docking ◽  
The Impact

AbstractMotivationGiven the importance of protein–ribonucleic acid (RNA) interactions in many biological processes, a variety of docking algorithms have been developed to predict the complex structure from individual protein and RNA partners in the past decade. However, due to the impact of molecular flexibility, the performance of current methods has hit a bottleneck in realistic unbound docking. Pushing the limit, we have proposed a protein-ensemble–RNA docking strategy to explicitly consider the protein flexibility in protein–RNA docking through an ensemble of multiple protein structures, which is referred to as MPRDock. Instead of taking conformations from MD simulations or experimental structures, we obtained the multiple structures of a protein by building models from its homologous templates in the Protein Data Bank (PDB).ResultsOur approach can not only avoid the reliability issue of structures from MD simulations but also circumvent the limited number of experimental structures for a target protein in the PDB. Tested on 68 unbound–bound and 18 unbound–unbound protein–RNA complexes, our MPRDock/DITScorePR considerably improved the docking performance and achieved a significantly higher success rate than single-protein rigid docking whether pseudo-unbound templates are included or not. Similar improvements were also observed when combining our ensemble docking strategy with other scoring functions. The present homology model-based ensemble docking approach will have a general application in molecular docking for other interactions.Availability and implementationhttp://huanglab.phys.hust.edu.cn/mprdock/Supplementary informationSupplementary data are available at Bioinformatics online.

scholarly journals Relationship between monomer packing and receptor binding domain pocket status in the spike trimer of SARS-CoV-2 variants

2021 ◽  
Author(s):  
Jim Warwicker
Keyword(s):  
Receptor Binding ◽  
Ph Dependence ◽  
Protein Structures ◽  
Binding Pocket ◽  
Spike Protein ◽  
Protein Charge ◽  
Neutral Ph ◽  
Binding Domains ◽  
Up States ◽  
The Relationship

Existence of a SARS-CoV-2 spike protein trimer form with closer packing between monomers when receptor binding domains (RBDs) are all down, locked as opposed to closed, has been associated with linoleic acid (LA) binding at neutral pH, or can occur at acidic pH in the absence of LA binding. The relationship between degree of closure of the LA binding pocket of the RBD, and monomer burial in the trimer, is examined for a range of spike protein structures, including those with D614G mutation, and that of the Delta variant (which also carries D614G). Some spike protein structures with this aspartic acid mutation show monomer packing approaching that of the locked form (at neutral pH, without LA binding) for two segments, a third (around the RBD) remains less closely packed. Analysis of other coronavirus RBD structures suggests that mutation of the RBD in spike protein of the Omicron variant could lead to LA binding pocket changes. It is proposed that these changes could lead to one of two consequences for the Omicron variant spike protein (which also has the D614G mutation), at neutral pH and without LA binding, either easier access to a locked form throughout that leads to cooperative transitions between all RBD down and all RBD up, or maintenance of a spike trimer with locked characteristics C-terminal to the RBD at the same time as the RBD is free to transit between down and up states. The situation may also be impacted by spike protein charge mutations in the Omicron lineage that alter pH-dependence around the RBD, in a similar way to the changes induced elsewhere by D614G.

The Basic Study on the Relationship between the Physical Properties of Coating Pigment and the Coated Paper Quality

2011 ◽  
Vol 65 (12) ◽  
pp. 1293-1297
Author(s):  
Keiko Hashiguchi ◽  
Takehiro Yoshimatsu ◽  
Masanori Kawashima
Keyword(s):  
Physical Properties ◽  
Coated Paper ◽  
Basic Study ◽  
The Relationship ◽  
Paper Quality

Optimize Mixing Process Parameters of Synchronous Rotor Mixer Based on Orthogonal Method

2012 ◽  
Vol 501 ◽  
pp. 442-447
Author(s):  
Ping Fu ◽  
Feng Bao Bai ◽  
Chuan Sheng Wang ◽  
Shan Hu Li
Keyword(s):  
Physical Properties ◽  
Process Parameters ◽  
Fill Factor ◽  
Cooling Water ◽  
Mixing Process ◽  
Rotor Speed ◽  
Orthogonal Method ◽  
Cooling Water Temperature ◽  
Vulcanized Rubber ◽  
The Relationship

In this paper adopting the orthogonal method, self-developed compound formulation had tested, and the relationship between the physical properties of vulcanized rubber and rectangular synchronous rotor mixer parameters had researched. The results showed that when the fill factor was 0.6, the rotor speed was 70r/min, cooling water temperature was 45 °C, pressure on the top bolt was 0.8Mpa, the physical properties of the vulcanized rubber was best.

scholarly journals Macromolecular Structure Databases: Past Progress and Future Challenges

1998 ◽  
Vol 54 (6) ◽  
pp. 1085-1094 ◽  
Author(s):  
Helge Weissig ◽  
Ilya N. Shindyalov ◽  
Philip E. Bourne
Keyword(s):  
Management Practices ◽  
Temporal Trends ◽  
Protein Structures ◽  
Data Bank ◽  
Macromolecular Structure ◽  
Paper Briefly ◽  
Future Challenges ◽  
Structure Databases ◽  
Full Discussion ◽  
Self Consistency

Databases containing macromolecular structure data provide a crystallographer with important tools for use in solving, refining and understanding the functional significance of their protein structures. Given this importance, this paper briefly summarizes past progress by outlining the features of the significant number of relevant databases developed to date. One recent database, PDB+, containing all current and obsolete structures deposited with the Protein Data Bank (PDB) is discussed in more detail. PDB+ has been used to analyze the self-consistency of the current (1 January 1998) corpus of over 7000 structures. A summary of those findings is presented (a full discussion will appear elsewhere) in the form of global and temporal trends within the data. These trends indicate that challenges exist if crystallographers are to provide the community with complete and consistent structural results in the future. It is argued that better information management practices are required to meet these challenges.

Oxidative Modification of Fibrinogen Affects Its Binding Activity to Glycoprotein (GP) IIb/IIIa

2009 ◽  
Vol 16 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Sermin Tetik ◽  
Kurtulus Kaya ◽  
M. Demir ◽  
Emel Eksioglu-Demiralp ◽  
Turay Yardimci
Keyword(s):  
Metal Ion ◽  
Degradation Products ◽  
Binding Capacity ◽  
Protein Structures ◽  
Human Platelets ◽  
Binding Activity ◽  
Oxidative Modification ◽  
Oxidized Fibrinogen ◽  
Protein Functions

Aim: Proteins are sensitive biomarkers of human diease condition associated with oxidative stress. Alteration of protein structures by oxidants may result in partial or complete loss of protein functions. We have investigated the effect of structural modifications induced by metal ion catalyzed oxidation of fibrinogen on its binding capacity to glycoprotein IIb/IIIa (GpIIb/IIIa) and human platelets. Methods: We identified and quantified of binding capacity of native and oxidized fibrinogen to its receptor in vitro by flow cytometer. Dityrosine formation on oxidized fibrinogen were detected spectrophotometrically. Elevated degradation products of fibrinogen after oxidation were revealed in the HPLC analysis. The native and oxidized fibrinogen were analyzed on mass spectrum upon digestion with tyripsin. Results: Oxidatively modified fibrinogen showed less binding activity than native fibrinogen to GpIIb/IIIa coated micro beads and human platelets whereas slightly higher binding capaticity to ADP induced stimulated platelets. Formation of dityrosines in the amino acid side chains of fibrinogen were observed upon oxidation. Decreased binding capacity of oxidized fibrinogen correlated with intensities of dityrosine formation. Oxidized fibrinogen had more ion-mass intensities at higher than native fibrinogen. Clinical implications: Important point is decreased of binding capacity of the oxidized fibrinogen to own receptor. The decreased rate of binding, leading to effect in the diseases of clot formation may acount for the association between oxidation of fibrinogen and the incidence of effect in human diseases.

Lack of relationship between wheat in vitro viscosity and digestibility parameters for pigs

1998 ◽  
Vol 1998 ◽  
pp. 32-32
Author(s):  
F.J. Lewis ◽  
J. McEvoy ◽  
K.J. McCracken
Keyword(s):  
Physical Properties ◽  
Nutritive Value ◽  
Wheat Variety ◽  
Growing Pigs ◽  
Variable Composition ◽  
Wheat Quality ◽  
Inexpensive Method ◽  
Metabolisable Energy ◽  
The Relationship

Whilst wheat is a major component in many pig diets it has the most variable composition of any of the cereals (Bolton & Blair, 1974) with wheat variety and the environment in which it was grown influencing its chemical and physical properties and thus nutritive value. A rapid and inexpensive method for prediction of nutritive value is thus needed to account for these variations in wheat composition. Viscosity is closely related to the soluble arabinoxylan content of wheat (Dusel et al., 1997) with a high in vitro wheat viscosity associated with a reduction in apparent metabolisable energy (AME) for poultry (Classen et al, 1995). The relationship between viscosity and nutritive value for pigs is therefore of interest. The present study investigated the effect of wheat quality measured by extract viscosity, on ileal and overall digestibility using the post-valve ‘T’ caecal (PVTC) canulation method in growing pigs.

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