A New Hybrid Model of Amino Acid Substitution for Protein Functional Classification

In this paper, a new hybrid model of amino acid substitution is developed and compared with the others in previous works. The results show that the new hybrid model can characterize the protein sequences very well by calculating Fisher weights, which can denote how much the variants contribute to the classification.

The43,000Growth - associated Protein Functions as a Negative Growth Regulator in Glioma.

Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocy-toma formation and progression.In an effort to identify novel gene expression changes associated with astrocytomaformation,which might reveal new potential targets for glioma therapeutic drug design,we used the B8-RAS-transgenic mouse astrocytoma model.Using multiplex gene expression profiling,we found that

Identification of key residues in protein functional movements by using molecular dynamics simulations combined with a perturbation-response scanning method

The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process.In the present work,the perturbation-response scanning method developed by our group was combined with the molecular dynamics(MD)simulation to identify the key residues controlling the functional movement of proteins.In our method,a physical quantity that is directly related to protein specific function was introduced,and then based on the MD simulation trajectories,the perturbation-response scanning method was used to identify the key residues for functional motions,in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein.Two protein systems,i.e.,the heat shock protein 70 and glutamine binding protein,were selected as case studies to validate the effectiveness of our method.Our calculated results are in good agreement with the experimental results.The location of the key residues in the two proteins are similar,indicating the similar mechanisms behind the performance of their biological functions.

In silico protein function prediction:the rise of machine learning-based approaches

Proteins function as integral actors in essential life processes,rendering the realm of protein research a fundamental domain that possesses the potential to propel advancements in pharmaceuticals and disease investigation.Within the context of protein research,an imperious demand arises to uncover protein functionalities and untangle intricate mechanistic underpinnings.Due to the exorbitant costs and limited throughput inherent in experimental investigations,computational models offer a promising alternative to accelerate protein function annotation.In recent years,protein pre-training models have exhibited noteworthy advancement across multiple prediction tasks.This advancement highlights a notable prospect for effectively tackling the intricate downstream task associated with protein function prediction.In this review,we elucidate the historical evolution and research paradigms of computational methods for predicting protein function.Subsequently,we summarize the progress in protein and molecule representation as well as feature extraction techniques.Furthermore,we assess the performance of machine learning-based algorithms across various objectives in protein function prediction,thereby offering a comprehensive perspective on the progress within this field.

QAUST:Protein Function Prediction Using Structure Similarity,Protein Interaction,and Functional Motifs

The number of available protein sequences in public databases is increasing exponentially.However,a sig-nificant percentage of these sequences lack functional annotation,which is essential for the understanding of how bio-logical systems operate.Here,we propose a novel method,Quantitative Annotation of Unknown STructure(QAUST),to infer protein functions,specifically Gene Ontology(GO)terms and Enzyme Commission(EC)numbers.QAUST uses three sources of information:structure information encoded by global and local structure similarity search,biological network information inferred by protein–protein interaction data,and sequence information extracted from functionally discriminative sequence motifs.These three pieces of information are combined by consensus averaging to make the final prediction.Our approach has been tested on 500 protein targets from the Critical Assessment of Functional Annotation(CAFA)benchmark set.The results show that our method provides accurate functional annotation and outperforms other prediction methods based on sequence similarity search or threading.We further demonstrate that a previously unknown function of human tripartite motif-containing 22(TRIM22)protein predicted by QAUST can be experimentally validated.

Structural changes of proteins in liver cirrhosis and consequential changes in their function

The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose.Posttranslational modifications(PTMs)design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose.PTMs can change under pathological conditions,giving rise to aberrant or overmodified proteins.Undesired changes in the structure of proteins most often accompany undesired changes in their function,such as reduced activity or the appearance of new effects.Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control.Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation,nitration,glycosylation,acetylation,and ubiquitination.Some of them predominantly affect proteins that remain in liver cells,whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation.Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases,including cirrhosis.This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.

ON NETWORK-BASED KERNEL METHODS FOR PROTEIN-PROTEIN INTERACTIONS WITH APPLICATIONS IN PROTEIN FUNCTIONS PREDICTION

Predicting protein functions is an important issue in the post-genomic era. This paper studies several network-based kernels including local linear embedding （LLE） kernel method, diffusion kernel and laplacian kernel to uncover the relationship between proteins functions and protein-protein interactions （PPI）. The author first construct kernels based on PPI networks, then apply support vector machine （SVM） techniques to classify proteins into different functional groups. The 5-fold cross validation is then applied to the selected 359 GO terms to compare the performance of different kernels and guilt-by-association methods including neighbor counting methods and Chi-square methods. Finally, the authors conduct predictions of functions of some unknown genes and verify the preciseness of our prediction in part by the information of other data source.

Chaos game representation of functional protein sequences,and simulation and multifractal analysis of induced measures

Investigating the biological function of proteins is a key aspect of protein studies. Bioinformatic methods become important for studying the biological function of proteins. In this paper, we first give the chaos game representation （CGR） of randomly-linked functional protein sequences, then propose the use of the recurrent iterated function systems （RIFS） in fractal theory to simulate the measure based on their chaos game representations. This method helps to extract some features of functional protein sequences, and furthermore the biological functions of these proteins. Then multifractal analysis of the measures based on the CGRs of randomly-linked functional protein sequences are performed. We find that the CGRs have clear fractal patterns. The numerical results show that the RIFS can simulate the measure based on the CGR very well. The relative standard error and the estimated probability matrix in the RIFS do not depend on the order to link the functional protein sequences. The estimated probability matrices in the RIFS with different biological functions are evidently different. Hence the estimated probability matrices in the RIFS can be used to characterise the difference among linked functional protein sequences with different biological functions. From the values of the Dq curves, one sees that these functional protein sequences are not completely random. The Dq of all linked functional proteins studied are multifractal-like and sufficiently smooth for the Cq （analogous to specific heat） curves to be meaningful. Furthermore, the Dq curves of the measure μ based on their CCRs for different orders to link the functional protein sequences are almost identical if q 〉 0. Finally, the Ca curves of all linked functional proteins resemble a classical phase transition at a critical point.

A Simulated Annealing Algorithm for Training Empirical Potential Functions of Protein Folding

In this paper are reported the local minimum problem by means of current greedy algorithm for training the empirical potential function of protein folding on 8623 non-native structures of 31 globular proteins and a solution of the problem based upon the simulated annealing algorithm. This simulated annealing algorithm is indispensable for developing and testing highly refined empirical potential functions.

Paracrine and endocrine actions of bone——the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts

The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin（SOST） that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or ＂osteokines＂from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin（OCN） secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2（LCN2） is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.

Proteomics-based analysis of functional proteins from fermented of compound wheat embryo Chinese medicine

Compound probiotics were used to ferment compound wheat embryo Chinesemedicine(CWECM)at 37°C for a given period,and the fermentation end pointwas determined based on pHvalue.The full spectrumof the proteinswithin the fermentation supernatant was determined by ion mass spectrometry,and then the fermentation was analyzed by proteomics.The difference of functional protein ofCWECMwas analyzed before and after fermentation.Additionally,the changes in flavor of peptides were examined.Our results indicated that when the fermentationwas performed for 96 h,the pH value became stable over time,which it shifted froman initial 3.98±0.04 to a stable 2.78±0.04.Proteomicbased analysis of the fermentation supernatant indicated that the fermentation of the probiotics increased.The amount of functional proteome and protein within the supernatant increased from 60 proteomes and 136 proteins before fermentation to 70 proteomes and 149 proteins post fermentation.These proteins were primarily members of the Ubiquitin and Histone families.These families contain more specific peptides after fermentation,and the coverage was reduced.Analysis of the unique P0C512 protein after fermentation indicated that this protein is an unstable,3Deffect columnar protein.We also found that probiotic fermentation can reduce the proportion of bitter peptideswithin fermentation broth from 47.49%to 36.98%,and the proportion of sweet peptides increased after fermentation from 35.29%to 51.01%.Based on testing,we concluded that fermentation of CWECM by compound probiotics can reduce the pH of the CWECM solution,increase the number of functional proteomes and proteins,improve the taste of CWECM solutions,and improve the therapeutic efficacy of CWECM.

High Protein Diet that Cause Weight Loss and Lower Blood Glucose Level Have a Serious Impact on the Kidney Functions of Male Diabetic Obese Albino Rats

Background: High protein (HP) diets are increasingly being recommended as one of the management strategies for weight control in overweight and obese individuals. The health benefits of high protein diets are well-established, but the mechanisms of action on body systems responsible for the changes in body weight and glycaemic control are not well-clear. Objective: The present study aimed to examine the effect of HP diets on the kidney functions of diabetic obese albino rats. Material and Methods: Eighty male adult male albino rats were used in this study. The animals were divided into eight equal groups (10 rats for each). Type 2 DM and obesity were induced. At the end of the 12 weeks, samples were collected for biochemical analysis. Results: The high protein diet led to significant decrease in BW, FI, BG, TC, LDL, TG, Lactate dehydrogenase, albumin, urine pH and urine citrate;while serum insulin, HDL, urea, creatinine, total protein, urine volume and urinary excretion of Ca were significantly higher in high protein diet groups. Conclusion: A high protein intake in diabetic obese albino rats for 12 weeks led to changes in the serum and urine levels of markers of renal function which indicated abnormalities in the functions of the kidney.

The biological function of type I receptors of bone morphogenetic protein in bone

Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.

Activated protein C: A regulator of human skin epidermal keratinocyte function

Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

Effects of Maixuekang Capsules Combined with Edaravone on Serum MMP-9, S-100β Protein Levels and Neurological Functions in Patients with Hemorrhagic Cerebral Infarction

OBJECTIVE: To investigate the effects of Maixuekang Capsules combined with edaravone on serum matrix metalloproteinase-9(MMP-9), S-100β protein levels and neurological functions in patients with hemorrhagic cerebral infarction. METHOSDS: A total of 76 patients with hemorrhagic cerebral infarction treated in the First Affiliated Hospital of Henan University of Science and Technology from January 2017 to May 2018 were selected and were randomly divided into treatment group and control group, with 38 patients in each group. The control group was given edaravone, and the treatment group was given Maixuekang Capsules on the basis of the control group. The clinical efficacy, serum MMP-9 and S-100β protein levels, neurological function recovery, activity of daily living and incidence rate of adverse reactions were compared between the 2 groups. RESULTS: The total effective rate of the treatment group was 92.11%, which was higher than 71.05% of the control group(P < 0.05); the National Institutes of Health Stroke Scale(NIHSS) score in the 2 groups decreased(P < 0.05), and the Activity of Daily Living Scale(ADL) score increased(P < 0.05), the improvement of the above 2 scores in the treatment group were better than those in the control group(P < 0.05); the level of MMP-9 was gradually decreasing in the 2 groups, on the 7th day, 14 th day after treatment, and the levels of MMP-9 decreased significantly(P < 0.05), and the treatment group was lower than the control group at all time points(P < 0.05); on the 3rd day after treatment, the levels of S-100β protein in the 2 groups increased significantly(P < 0.05); on the 7th day, 14 th day after treatment, the levels of S-100β protein in the two groups decreased significantly(P < 0.05), and the treatment group was significantly lower than the control group(P < 0.05); there was no significant difference in incidence rate of adverse reactions between 7.89% in the control group and 5.26% in the treatment group(P > 0.05). CONCLUSION: The combination of Maixuekang Capsules and edaravone is effective in treating hemorrhagic cerebral infarction, and it can significantly improve neurological function defect and daily living ability, reduce serum MMP-9 and S-100β protein levels, and has higher safety.

The Effect of Hydrolysis with Neutrase on Molecular Weight,Functional Properties,and Antioxidant Activities of Alaska Pollock Protein Isolate

In this study, the Alaska pollock protein isolate(APPI) was hydrolyzed by Neutrase for 20, 40, 80, 120, 160, 200, and 240 min. Hydrolysates with different molecular weights were produced and they were named as H1–H7. Furthermore, the effects of hydrolysis on the average molecular weights, functional properties(solubility, oil-holding capacities, foaming activities, and emulsifying properties), and antioxidant activities(1, 1-diphenyl-2-picrylhydrazyl, superoxide, and hydroxyl free radical-scavenging activities) were determined. It was found that when the degree of hydrolysis(DH) increased, the average molecular weights of the hydrolysates decreased significantly. The functional properties of APPI were also significantly improved. The hydrolysates of APPI exhibited better solubility, emulsifying activities, and foaming activities. Hydrolysates with low molecular weights(<1 kDa) had better solubility, oil-holding capacities, and emulsifying activities, while hydrolysates with higher molecular weights(>1 kDa) had better foaming activities. In addition, the hydrolysates exhibited excellent antioxidant properties, while the inhibition values of 1, 1-diphenyl-2-picryl hydroxyl(DPPH), superoxide, and hydroxyl free radical-scavenging activities, were 85.22%, 53.56%, and 75.00% respectively, when the concentration of the hydrolysates was 5.0 mg mL^(-1). The lower the average molecular weight was, the higher was the antioxidant activity. These results indicated that hydrolysis with Neutrase is an effective method for improving the functional and antioxidant properties of APPI. The hydrolysates of APPI displayed great potentials to be used as natural antioxidants in protein-rich aqueous foods such as nutrient supplements and sports beverages.

Insect heat shock proteins and their underlying functions

Considering huge number of insect species in the world,studies of heat shock proteins on insects are still very limited.Special focus of＂Insect heat shock proteins and their underlying functions＂provides a comprehensive knowledge for the given topics,which focuses on the heat shock proteins from four insect species：i）Five heat shock proteins（HSPs）from Cotesia chilonis were identified,and their expressional patterns under different temperatures were examined.