EyeCNN: exploring the potential of convolutional neural networks for identification of multiple eye diseases through retinal imagery.

BACKGROUND: The eyes are the most important part of the human body as these are directly connected to the brain and help us perceive the imagery in daily life whereas, eye diseases are mostly ignored and underestimated until it is too late. Diagnosing eye disorders through manual diagnosis by the physician can be very costly and time taking. OBJECTIVE: Thus, to tackle this, a novel method namely EyeCNN is proposed for identifying eye diseases through retinal images using EfficientNet B3. METHODS: A dataset of retinal imagery of three diseases, i.e. Diabetic Retinopathy, Glaucoma, and Cataract is used to train 12 convolutional networks while EfficientNet B3 was the topperforming model out of all 12 models with a testing accuracy of 94.30%. RESULTS: After preprocessing of the dataset and training of models, various experimentations were performed to see where our model stands. The evaluation was performed using some well-defined measures and the final model was deployed on the Streamlit server as a prototype for public usage. The proposed model has the potential to help diagnose eye diseases early, which can facilitate timely treatment. CONCLUSION: The use of EyeCNN for classifying eye diseases has the potential to aid ophthalmologists in diagnosing conditions accurately and efficiently. This research may also lead to a deeper understanding of these diseases and it may lead to new treatments. The webserver of EyeCNN can be accessed at ( https://abdulrafay97-eyecnn-app-rd9wgz.streamlit.app/ ).

ORI-Deep: improving the accuracy for predicting origin of replication sites by using a blend of features and long short-term memory network.

Replication of DNA is an important process for the cell division cycle, gene expression regulation and other biological evolution processes. It also has a crucial role in a living organism's physical growth and structure. Replication of DNA comprises of three stages known as initiation, elongation and termination, whereas the origin of replication sites (ORI) is the location of initiation of the DNA replication process. There exist various methodologies to identify ORIs in the genomic sequences, however, these methods have used either extensive computations for execution, or have limited optimization for the large datasets. Herein, a model called ORI-Deep is proposed to identify ORIs from the multiple cell type genomic sequence benchmark data. An efficient method is proposed using a deep neural network to identify ORIs for four different eukaryotic species. For better representation of data, a feature vector is constructed using statistical moments for the training and testing of data and is further fed to a long short-term memory (LSTM) network. To prove the effectiveness of the proposed model, we applied several validation techniques at different levels to obtain seven accuracy metrics, and the accuracy score for self-consistency, 10-fold cross-validation, jackknife and the independent set test is observed to be 0.977, 0.948, 0.976 and 0.977, respectively. Based on the results, it can be concluded that ORI-Deep can efficiently predict the sites of origin replication in DNA sequence with high accuracy. Webserver for ORI-Deep is available at (https://share.streamlit.io/waqarhusain/orideep/main/app.py), whereas source code is available at (https://github.com/WaqarHusain/OriDeep).

sAMP-PFPDeep: Improving accuracy of short antimicrobial peptides prediction using three different sequence encodings and deep neural networks.

Short antimicrobial peptides (sAMPs) belong to a significant repertoire of antimicrobial agents and are known to possess enhanced antimicrobial activity, higher stability and less toxicity to human cells, as well as less complex than other large biological drugs. As these molecules are significantly important, herein, a prediction method for sAMPs (with a sequence length ≤ 30 residues) is proposed for accurate and efficient prediction of sAMPs instead of laborious and costly experimental approaches. Benchmark dataset was collected from a recently reported study and sequences were converted into three channel images comprising information related to the position, frequency and sum of 12 physiochemical features as the first, second and third channels, respectively. Two image-based deep neural networks (DNNs), i.e. RESNET-50 and VGG-16 were trained and evaluated using various metrics while a comparative analysis with previous techniques was also performed. Validation of sAMP-PFPDeep was also performed by using molecular docking based analysis. The results showed that VGG-16 provided more accurate results, i.e. 98.30% training accuracy and 87.37% testing accuracy for predicting sAMPs as compared to those of RESNET-50 having 96.14% training accuracy and 83.87% testing accuracy. However, the comparative analysis revealed that both these models outperformed previously reported state-of-the-art methods. Based on the results, it is concluded that sAMP-PFPDeep can help identify antimicrobial peptides with promising accuracy and efficiency. It can help biologists and scientists to identify antimicrobial peptides, by further aiding the computer-aided drug design and discovery, as well as virtual screening protocols against various pathologies. sAMP-PFPDeep is available at (https://github.com/WaqarHusain/sAMP-PFPDeep).

iPhosS(Deep)-PseAAC: Identification of Phosphoserine Sites in Proteins Using Deep Learning on General Pseudo Amino Acid Compositions.

Among all the PTMs, the protein phosphorylation is pivotal for various pathological and physiological processes. About 30 percent of eukaryotic proteins undergo the phosphorylation modification, leading to various changes in conformation, function, stability, localization, and so forth. In eukaryotic proteins, phosphorylation occurs on serine (S), Threonine (T) and Tyrosine (Y) residues. Among these all, serine phosphorylation has its own importance as it is associated with various importance biological processes, including energy metabolism, signal transduction pathways, cell cycling, and apoptosis. Thus, its identification is important, however, the in vitro, ex vivo and in vivo identification can be laborious, time-taking and costly. There is a dire need of an efficient and accurate computational model to help researchers and biologists identifying these sites, in an easy manner. Herein, we propose a novel predictor for identification of Phosphoserine sites (PhosS) in proteins, by integrating the Chou's Pseudo Amino Acid Composition (PseAAC) with deep features. We used well-known DNNs for both the tasks of learning a feature representation of peptide sequences and performing classifications. Among different DNNs, the best score is shown by Covolutional Neural Network based model which renders CNN based prediction model the best for Phosphoserine prediction. Based on these results, it is concluded that the proposed model can help to identify PhosS sites in a very efficient and accurate manner which can help scientists understand the mechanism of this modification in proteins.

Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies.

The recent COVID-19 pandemic has impacted nearly the whole world due to its high morbidity and mortality rate. Thus, scientists around the globe are working to find potent drugs and designing an effective vaccine against COVID-19. Phytochemicals from medicinal plants are known to have a long history for the treatment of various pathogens and infections; thus, keeping this in mind, this study was performed to explore the potential of different phytochemicals as candidate inhibitors of the HR1 domain in SARS-CoV-2 spike protein by using computer-aided drug discovery methods. Initially, the pharmacological assessment was performed to study the drug-likeness properties of the phytochemicals for their safe human administration. Suitable compounds were subjected to molecular docking to screen strongly binding phytochemicals with HR1 while the stability of ligand binding was analyzed using molecular dynamics simulations. Quantum computation-based density functional theory (DFT) analysis was constituted to analyze the reactivity of these compounds with the receptor. Through analysis, 108 phytochemicals passed the pharmacological assessment and upon docking of these 108 phytochemicals, 36 were screened passing a threshold of -8.5 kcal/mol. After analyzing stability and reactivity, 5 phytochemicals, i.e., SilybinC, Isopomiferin, Lycopene, SilydianinB, and Silydianin are identified as novel and potent candidates for the inhibition of HR1 domain in SARS-CoV-2 spike protein. Based on these results, it is concluded that these compounds can play an important role in the design and development of a drug against COVID-19, after an exhaustive in vitro and in vivo examination of these compounds, in future.

Biological perspective of thiazolide derivatives against Mpro and MTase of SARS-CoV-2: Molecular docking, DFT and MD simulation investigations.

Humans around the globe have been severely affected by SARS-CoV-2 and no treatment has yet been authorized for the treatment of this severe condition brought by COVID-19. Here, an in silico research was executed to elucidate the inhibitory potential of selected thiazolides derivatives against SARS-CoV-2 Protease (Mpro) and Methyltransferase (MTase). Based on the analysis; 4 compounds were discovered to have efficacious and remarkable results against the proteins of the interest. Primarily, results obtained through this study not only allude these compounds as potential inhibitors but also pave the way for in vivo and in vitro validation of these compounds.

A hybrid deep neural network for classification of schizophrenia using EEG Data.

Schizophrenia is a serious mental illness that causes great harm to patients, so timely and accurate detection is essential. This study aimed to identify a better feature to represent electroencephalography (EEG) signals and improve the classification accuracy of patients with schizophrenia and healthy controls by using EEG signals. Our research method involves two steps. First, the EEG time series is preprocessed, and the extracted time-domain and frequency-domain features are transformed into a sequence of red-green-blue (RGB) images that carry spatial information. Second, we construct hybrid deep neural networks (DNNs) that combine convolution neural networks and long short-term memory to address RGB images to classify schizophrenic patients and healthy controls. The results show that the fuzzy entropy (FuzzyEn) feature is more significant than the fast Fourier transform (FFT) feature in brain topography. The deep learning (DL) method that we propose achieves an average accuracy of 99.22% with FuzzyEn and an average accuracy of 96.34% with FFT. These results show that the best effect is to extract fuzzy features as input features from EEG time series and then use a hybrid DNN for classification. Compared with the most advanced methods in this field, significant improvements have been achieved.

iDRP-PseAAC: Identification of DNA Replication Proteins Using General PseAAC and Position Dependent Features.

DNA replication is one of the specific processes to be considered in all the living organisms, specifically eukaryotes. The prevalence of DNA replication is significant for an evolutionary transition at the beginning of life. DNA replication proteins are those proteins which support the process of replication and are also reported to be important in drug design and discovery. This information depicts that DNA replication proteins have a very important role in human bodies, however, to study their mechanism, their identification is necessary. Thus, it is a very important task but, in any case, an experimental identification is time-consuming, highly-costly and laborious. To cope with this issue, a computational methodology is required for prediction of these proteins, however, no prior method exists. This study comprehends the construction of novel prediction model to serve the proposed purpose. The prediction model is developed based on the artificial neural network by integrating the position relative features and sequence statistical moments in PseAAC for training neural networks. Highest overall accuracy has been achieved through tenfold cross-validation and Jackknife testing that was computed to be 96.22% and 98.56%, respectively. Our astonishing experimental results demonstrated that the proposed predictor surpass the existing models that can be served as a time and cost-effective stratagem for designing novel drugs to strike the contemporary bacterial infection.

Using CHOU'S 5-Steps Rule to Predict O-Linked Serine Glycosylation Sites by Blending Position Relative Features and Statistical Moment.

Glycosylation of proteins in eukaryote cells is an important and complicated post-translation modification due to its pivotal role and association with crucial physiological functions within most of the proteins. Identification of glycosylation sites in a polypeptide chain is not an easy task due to multiple impediments. Analytical identification of these sites is expensive and laborious. There is a dire need to develop a reliable computational method for precise determination of such sites which can help researchers to save time and effort. Herein, we propose a novel predictor namely iGlycoS-PseAAC by integrating the Chou's Pseudo Amino Acid Composition (PseAAC) and relative/absolute position-based features. The self-consistency results show that the accuracy revealed by the model using the benchmark dataset for prediction of O-linked glycosylation having serine sites is 98.8 percent. The overall accuracy of predictor achieved through 10-fold cross validation by combining the positive and negative results is 97.2 percent. The overall accuracy achieved through Jackknife test is 96.195 percent by aggregating of all the prediction results. Thus the proposed predictor can help in predicting the O-linked glycosylated serine sites in an efficient and accurate way. The overall results show that the accuracy of the iGlycoS-PseAAC is higher than the existing tools.

iPhosH-PseAAC: Identify Phosphohistidine Sites in Proteins by Blending Statistical Moments and Position Relative Features According to the Chou's 5-Step Rule and General Pseudo Amino Acid Composition.

Protein phosphorylation is one of the key mechanism in prokaryotes and eukaryotes and is responsible for various biological functions such as protein degradation, intracellular localization, the multitude of cellular processes, molecular association, cytoskeletal dynamics, and enzymatic inhibition/activation. Phosphohistidine (PhosH) has a key role in a number of biological processes, including central metabolism to signalling in eukaryotes and bacteria. Thus, identification of phosphohistidine sites in a protein sequence is crucial, and experimental identification can be expensive, time-taking, and laborious. To address this problem, here, we propose a novel computational model namely iPhosH-PseAAC for prediction of phosphohistidine sites in a given protein sequence using pseudo amino acid composition (PseAAC), statistical moments, and position relative features. The results of the proposed predictor are validated through self-consistency testing, 10-fold cross-validation, and jackknife testing. The self-consistency validation gave the 100 percent accuracy, whereas, for cross-validation, the accuracy achieved is 94.26 percent. Moreover, jackknife testing gave 97.07 percent accuracy for the proposed model. Thus, the proposed model iPhosH-PseAAC for prediction of iPhosH site has the great ability to predict the PhosH sites in given proteins.

Analysis of Inhibitor Binding Combined with Reactivity Studies to Discover the Potentially Inhibiting Phytochemicals Targeting Chikungunya Viral Replication.

BACKGROUND: Chikungunya fever is a challenging threat to human health in various parts of the world nowadays. Many attempts have been made for developing an effective drug against this viral disease and no effective antiviral treatment has been developed to control the spread of the Chikungunya virus (CHIKV) in humans. OBJECTIVE: This research is aimed at the discovery of potential inhibitors against this virus by employing computational techniques to study the interactions between non-structural proteins of Chikungunya virus and phytochemicals from plants. METHODS: Four non-structural proteins were docked with 2035 phytochemicals from various plants. The ligands having binding energies ≥ -8.0 kcal/mol were considered as potential inhibitors for these proteins. ADMET studies were also performed to analyze different pharmacological properties of these docked compounds and to further analyze the reactivity of these phytochemicals against CHIKV, DFT analysis was carried out based on HOMO and LUMO energies. RESULTS: By analyzing the binding energies, Ki, ADMET properties and band energy gaps, it was observed that 13 phytochemicals passed all the criteria to be a potent inhibitor against CHIKV in humans. CONCLUSION: A total of 13 phytochemicals were identified as potent inhibiting candidates, which can be used against the Chikungunya virus.

Optimization of serine phosphorylation prediction in proteins by comparing human engineered features and deep representations.

Deep representations can be used to replace human-engineered representations, as such features are constrained by certain limitations. For the prediction of protein post-translation modifications (PTMs) sites, research community uses different feature extraction techniques applied on Pseudo amino acid compositions (PseAAC). Serine phosphorylation is one of the most important PTM as it is the most occurring, and is important for various biological functions. Creating efficient representations from large protein sequences, to predict PTM sites, is a time and resource intensive task. In this study we propose, implement and evaluate use of Deep learning to learn effective protein data representations from PseAAC to develop data driven PTM detection systems and compare the same with two human representations.. The comparisons are performed by training an xgboost based classifier using each representation. The best scores were achieved by RNN-LSTM based deep representation and CNN based representation with an accuracy score of 81.1% and 78.3% respectively. Human engineered representations scored 77.3% and 74.9% respectively. Based on these results, it is concluded that the deep features are promising feature engineering replacement to identify PhosS sites in a very efficient and accurate manner which can help scientists understand the mechanism of this modification in proteins.

Insights into Machine Learning-based Approaches for Virtual Screening in Drug Discovery: Existing Strategies and Streamlining Through FP-CADD.

BACKGROUND: Machine learning is an active area of research in computer science by the availability of big data collection of all sorts prompting interest in the development of novel tools for data mining. Machine learning methods have wide applications in computer-aided drug discovery methods. Most incredible approaches to machine learning are used in drug designing, which further aid the process of biological modelling in drug discovery. Mainly, two main categories are present which are Ligand-Based Virtual Screening (LBVS) and Structure-Based Virtual Screening (SBVS), however, the machine learning approaches fall mostly in the category of LBVS. OBJECTIVES: This study exposits the major machine learning approaches being used in LBVS. Moreover, we have introduced a protocol named FP-CADD which depicts a 4-steps rule of thumb for drug discovery, the four protocols of computer-aided drug discovery (FP-CADD). Various important aspects along with SWOT analysis of FP-CADD are also discussed in this article. CONCLUSION: By this thorough study, we have observed that in LBVS algorithms, Support Vector Machines (SVM) and Random Forest (RF) are those which are widely used due to high accuracy and efficiency. These virtual screening approaches have the potential to revolutionize the drug designing field. Also, we believe that the process flow presented in this study, named FP-CADD, can streamline the whole process of computer-aided drug discovery. By adopting this rule, the studies related to drug discovery can be made homogeneous and this protocol can also be considered as an evaluation criterion in the peer-review process of research articles.

Phytochemicals from Selective Plants Have Promising Potential against SARS-CoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations.

Coronaviruses have been reported previously due to their association with the severe acute respiratory syndrome (SARS). After SARS, these viruses were known to be causing Middle East respiratory syndrome (MERS) and caused 35% evanescence amid victims pursuing remedial care. Nowadays, beta coronaviruses, members of Coronaviridae, family order Nidovirales, have become subjects of great importance due to their latest pandemic originating from Wuhan, China. The virus named as human-SARS-like coronavirus-2 contains four structural as well as sixteen nonstructural proteins encoded by single-stranded ribonucleic acid of positive polarity. As there is no vaccine available to treat the infection caused by these viruses, there is a dire need for taking necessary steps against this virus. Herein, we have targeted two nonstructural proteins of SARS-CoV-2, namely, methyltransferase (nsp16) and helicase (nsp13), respectively, due to their substantial activity in viral pathogenesis. A total of 2035 compounds were analyzed for their pharmacokinetics and pharmacological properties. The screened 108 compounds were docked against both targeted proteins and were compared with previously reported known compounds. Compounds with high binding affinity were analyzed for their reactivity through DFT analysis, and binding was analyzed using molecular dynamics simulations. Through the analyses performed in this study, it is concluded that EryvarinM, Silydianin, Osajin, and Raddeanine can be considered potential inhibitors for MTase, while TomentodiplaconeB, Osajin, Sesquiterpene Glycoside, Rhamnetin, and Silydianin for helicase after these compounds are validated thoroughly using in vitro and in vivo protocols.

ADVIT: Using the potentials of deep representations incorporated with grid-based features of dorsum vein patterns for human identification.

The identification of an individual is one of the main applications of forensic science, used in legal settings for deciding cases in courts of law. Different methods have been developed for the identification of a person, including fingerprints, DNA profiling, retina scan, facial features and many others. The reliable and accurate identification mainly relies upon substantial variability of structures and features of evidence corresponding to reference material. During the last decade, human identification through hand vein patterns has been focused in various studies and shown promising results. However, most of the reported methods require extensive human efforts for manual feature calculation. Herein, we propose a novel identification tool namely ADVIT for the identification of humans based on their dorsum veins pattern. The samples of the dorsum of the right or left hand were collected from 50 participants in the form of images. Initially, images were preprocessed and noise (in terms of hair on the skin and other details) was removed. Later on, the vein skeleton was extracted from the preprocessed images and a binary image of veins pattern (veins in the foreground and every other detail as background) was generated. Two different types of the feature were computed and based on these features, three different experiments were performed and the evaluation metrics were computed. Merging of hand-crafted grid-based features and deep representation from RESNET-50 showed maximum results in terms of Sensitivity (0.8803), Specificity (0.8890), Precision (0.8849), False Positive Rate (0.1074), Accuracy (0.8861), F1 Score (0.8817), and MCC (0.7636). These results depicted that the model is accurate and sensitive for identification through dorsum veins pattern. The proposed model can aid forensic scientists to identify perpetrator using hand images. ADVIT is freely available at (http://zeetu.org/advit.html).

Insights into the inhibitory potential of selective phytochemicals against Mpro of 2019-nCoV: a computer-aided study.

At the end of December 2019, a novel strain of coronavirus, given the name of 2019-nCoV, emerged for exhibiting symptoms of severe acute respiratory syndrome. The virus is spreading rapidly in China and around the globe, affecting thousands of people leading to a pandemic. To control the mortality rate associated with the 2019-nCoV, prompt steps are needed. Until now there is no effective treatment or drug present to control its life-threatening effects in the humans. The scientist is struggling to find new inhibitors of this deadly virus. In this study, to identify the effective inhibitor candidates against the main protease (Mpro) of 2019-nCoV, computational approaches were adopted. Phytochemicals having immense medicinal properties as ligands were docked against the Mpro of 2019-nCoV to study their binding properties. ADMET and DFT analyses were also further carried out to analyze the potential of these phytochemicals as an effective inhibitor against Mpro of 2019-nCoV.

A Sequence-Based Predictor of Zika Virus Proteins Developed by Integration of PseAAC and Statistical Moments.

BACKGROUND: ZIKV has been a well-known global threat, which hits almost all of the American countries and posed a serious threat to the entire globe in 2016. The first outbreak of ZIKV was reported in 2007 in the Pacific area, followed by another severe outbreak, which occurred in 2013/2014 and subsequently, ZIKV spread to all other Pacific islands. A broad spectrum of ZIKV associated neurological malformations in neonates and adults has driven this deadly virus into the limelight. Though tremendous efforts have been focused on understanding the molecular basis of ZIKV, the viral proteins of ZIKV have still not been studied extensively. OBJECTIVES: Herein, we report the first and the novel predictor for the identification of ZIKV proteins. METHODS: We have employed Chou's pseudo amino acid composition (PseAAC), statistical moments and various position-based features. RESULTS: The predictor is validated through 10-fold cross-validation and Jackknife testing. In 10- fold cross-validation, 94.09% accuracy, 93.48% specificity, 94.20% sensitivity and 0.80 MCC were achieved while in Jackknife testing, 96.62% accuracy, 94.57% specificity, 97.00% sensitivity and 0.88 MCC were achieved. CONCLUSION: Thus, ZIKVPred-PseAAC can help in predicting the ZIKV proteins efficiently and accurately and can provide baseline data for the discovery of new drugs and biomarkers against ZIKV.

Abnormal Anatomical Rich-Club Organization and Structural-Functional Coupling in Mild Cognitive Impairment and Alzheimer's Disease.

Emerging research indicates interruptions in the wiring organization of the brain network in Mild cognitive impairment (MCI) and Alzheimer's disease (AD). Due to the important role of rich-club organization in distinguishing abnormalities of AD patients and the close relationship between structural connectivity (SC) and functional connectivity (FC), our study examined whether changes in SC-FC coupling and the relationship with abnormal rich-club organizations during the development of diseases may contribute to the pathophysiology of AD. Structural diffusion-tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) were performed in 38 normal controls (NCs), 40 MCI patients and 19 AD patients. Measures of the rich-club structure and its role in global structural-functional coupling were administered. Our study found decreased levels of feeder and local connectivity in MCI and AD patients, which were the main contributing factors to the lower efficiency of the brain structural network. Another important finding was that we have more accurately characterized the changing pattern of functional brain dynamics. The enhanced coupling between SC and FC in MCI and AD patients might be due to disruptions in optimal structural organization. More interestingly, we also found increases in the SC-FC coupling for feeder and local connections in MCI and AD patients. SC-FC coupling also showed significant differences between MCI and AD patients, mainly between the abnormal feeder connections. The connection density and coupling strength were significantly correlated with clinical metrics in patients. The present findings enhanced our understanding of the neurophysiologic mechanisms associated with MCI and AD.

ForeStatistics: A windows-based feature-rich software program for performing statistics in forensic DNA analysis, paternity and relationship testing.

Forensic science is one of the most modern and applied fields of science, today and comprises of various domains. These include Fingerprints analysis, Questioned document analysis, Forensic DNA and serology, Anthropometry, Cyber and Digital forensics, and many other fields. All these fields aid the process of decision making in the courts of law and legal settings; however, DNA profiling and its analyses are one of the most important aspects of forensic science today. In Forensic DNA analysis, the statistical calculations are very important to estimate the conclusiveness of DNA evidence in forensic cases; and to establish paternity and relatedness in civil and criminal matters. These statistics, when performed manually, leave a chance of error or ambiguity in the calculation, and are hectic and time-taking. Therefore, the computer-aided approaches are opted in forensics to perform DNA statistics calculations. Keeping its importance in mind, a highly accurate windows-based software program namely ForeStatistics is proposed in this study. ForeStatistics is rich in features such as DNA statistical calculations, DNA profile management and its matching. The software can estimate random match probabilities for single-source profiles, combined probability of inclusion for mixed profiles, paternity index of a disputed child in duo and trio cases, paternity of the disputed child when the alleged father is related to mother or biological father and relatedness in cases of grandparents/grandchild, avuncular relation and cousin. It is validated through different protocols and the validation of ForeStatistics depicts that it is highly accurate in terms of performing DNA statistics or DNA profile matching. Thus, it is concluded, that ForeStatistics has a great utility in the field of Forensic DNA analysis and can help DNA scientists, in performing various DNA related statistics, accurately and very efficiently. ForeStatistics can be downloaded freely from (http://zeetu.org/forestatistics.html).

In Silico Inhibition of BACE-1 by Selective Phytochemicals as Novel Potential Inhibitors: Molecular Docking and DFT Studies.

BACKGROUND: Alzheimer's Disease (AD) has become the most common age-dependent disease of dementia. The trademark pathologies of AD are the presence of amyloid aggregates in neurofibrils. Recently phytochemicals being considered as potential inhibitors against various neurodegenerative, antifungal, antibacterial and antiviral diseases in human beings. OBJECTIVE: This study targets the inhibition of BACE-1 by phytochemicals using in silico drug discovery analysis. METHODS: A total of 3150 phytochemicals were collected from almost 25 different plants through literature assessment. The ADMET studies, molecular docking and density functional theory (DFT) based analysis were performed to analyze the potential inhibitory properties of these phytochemicals. RESULTS: The ADMET and docking results exposed seven compounds that have high potential as an inhibitory agent against BACE-1 and show binding affinity >8.0 kcal/mol against BACE-1. They show binding affinity greater than those of various previously reported inhibitors of BACE-1. Furthermore, DFT based analysis has shown high reactivity for these seven phytochemicals in the binding pocket of BACE- 1, based on ELUMO, EHOMO and Kohn-Sham energy gap. All seven phytochemicals were testified (as compared to experimental ones) as novel inhibitors against BACE-1. CONCLUSION: Out of seven phytochemicals, four were obtained from plant Glycyrrhiza glabra i.e. Shinflavanone, Glabrolide, Glabrol and PrenyllicoflavoneA, one from Huperzia serrate i.e. Macleanine, one from Uncaria rhynchophylla i.e. 3a-dihydro-cadambine and another one was from VolvalerelactoneB from plant Valeriana-officinalis. It is concluded that these phytochemicals are suitable candidates for drug/inhibitor against BACE-1, and can be administered to humans after experimental validation through in vitro and in vivo trials.