BIOINFORMATICS AND COMPUTATIONAL BIOLOGY

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BCB-01

AUTOMATIC RECOGNITION OF CENTRAL VEIN AND SINUSOIDS IN RAT LIVER HISTOPATHOLOGICAL IMAGES FOR DAMAGE ASSESSMENT CAUSED BY ALCOHOL

James Patrick A. Acang, Doreen D. Domingo, Enoch Caryl B. Taclan, and Donna Mae B. Fronda
ABSTRACT

​Chronic-binge alcohol consumption is a leading cause of chronic liver disease worldwide.  This disease could lead to cirrhosis and hepatocellular carcinoma. Prolonged alcohol drinking significantly affects the liver, kidney, pancreas, heart, lungs, Central Nervous System (CNS), and other organs, as reported by recent work in literature.  Building a tool for assessing and quantifying these damages could provide a different perspective on medical diagnosis.  This work is part of the effort of infusing computational biology in medical diagnosis.  In this research, we investigated how to detect the Central Vein and Sinusoids automatically by a computer.  Based on the literature, the Central Vein and Sinusoids are a few of the liver morpho-anatomical parts affected by alcohol. Detecting these parts automatically could revolutionize the damage estimation in the liver.  We composed our dataset from the Michigan Histology and Virtual Microscopy Learning Resource.  One hundred histopathological images were collected and were processed for analysis.  These histopathological images were manually cropped using 40x.svs (Scan Scope Virtual Slide) magnification and were manually labeled and annotated for ground truth comparison and performance analysis.  Sixty percent (60%) of the dataset was used for training, and the other forty percent (40%) were used for testing.  Gaussian and thresholding filters were used for the recognizer.  Our initial results show that the model could meet 90% pixel accuracy in detecting the Central Vein and Sinusoids in the Histopathological images.  This finding shows promising development in the field of medical diagnosis.
BCB-02

MICROARRAY ANALYSIS OF MR7-3, HIGH AMINO ACID RICE,
​DURING SEED DEVELOPMENT

Nogoy, Franz Marielle C., Sandoval, Sophia S., Campilan, Joni Rey H., Tablizo, Francis A., and Cho, Yong-Gu
ABSTRACT

​MR7-3, a stable mutant line from mature Korean cultivar Donganbyeo (WT) subjected to 70 Gy, was known to have a 20 times greater amino acid content but chalky grain quality. To elucidate the transcriptional changes in MR7-3, microarray data generated from RiceXPro using 5, 10, 15, and 20 days after pollination (DAP) grain developmental stages of WT and MR7-3 were analyzed. Differentially expressed genes (DEGs) were filtered using the limma package for R using the following conditions: p-value  0.05, fold change (FC) ≥ 2, and false discovery rate  0.05 using a Benjamini-Hochberg correction. There were 43, 245, 338 and 661 DEGs found in 5, 10, 15, and 20 DAP, respectively. Gene ontology of DEGs using Panther classification showed that most of the DEGs belong to catalytic activity (GO:0003824) in terms of molecular function, metabolic (GO:0008152) for the biological process, and most of the DEGs belong to cells (GO:0005623). DEGs were mapped in the KEGG database for pathway analysis to showchanges in the starch and sucrose metabolism pathways as well as in the biosynthesis of amino acids. Coexpression analysis was conducted to show possible connections between the high amino acid content and chalkiness in rice grains using a weighted correlation network analysis via the WGCNA package for R. Through coexpression analysis, it was revealed that known gene related to chalkiness, AGPase, found in the starch and sucrose metabolism pathway, was highly correlated to threonine aldolase and chorismate mutase, both found in the biosynthesis of amino acids pathway. Connecting and related pathways between the two are glycolysis and gluconeogenesis, suggesting it is worth looking into these pathways for more concrete explanations between the relationship of amino acid content and chalkiness. These insights on the gene expression of chalky rice with high amino acid content are integral to further understand and improve the quality and nutrition of rice.

Keywords: rice microarray, gene ontology, network pathways, coexpression analysis, amino acid content, chalkiness, grain development.
BCB-03

COMPARISON OF AFFINITIES BETWEEN TWO INTEGRIN α6 SUBUNIT BINDING PARTNERS THROUGH IN SILICO ANALYSIS

Amira Gabrielle M. Cantos, Kim Ivan A. Abesamis, Camille Anne S. Bagoyo, and Neil Andrew D. Bascos
ABSTRACT

​Integrins are a family of cell-surface receptors that mediate cell-matrix and cell-cell adhesion.  Each member is a heterodimer comprised of non-covalently associated alpha and beta subunits, whose identities in each integrin direct ligand specificities and function. In vertebrates, 18α and 8β subunits associate to form 24 unique heterodimers. The α6 integrin subunit pairs with either β1 or β4, but both heterodimers are receptors for laminin. Neither α6β1 nor α6β4 have deposited crystal structures. In this study, the structures of the ligand-binding domains (LBDs) of integrins α6β1 and α6β4 were predicted, and these models were analyzed computationally. In silico Alanine substitutions across the protein sequence predicted hotspots of interaction primarily at Tyr, Asp, and Arg residues for both β1 and β4. To compare the two α6 integrins, the models of the LBDs of α6β1 and α6β4 were assessed based on inter-subunit binding affinity. This was predicted to be higher for α6β4, which may be attributed to its role in promoting cellular adhesion and maintaining stability in the intermediate filament system. To determine the behavior of α6β1 and α6β4 in different environments, the models were equilibrated in NaCl and CaCl2. In agreement with binding affinity predictions, steered molecular dynamics (SMD) yielded higher rupture forces for α6β4 than for α6β1 in both environments. The rupture force of α6β1 was higher in NaCl (4658.61 kJ mol-1 nm-1) than in CaCl2 (4349.82 kJ mol-1 nm-1), which may be explained by the greater number of H-bonds and larger inter-subunit binding interface exhibited by α6β1 in NaCl. In contrast, α6β4 separates later and with a greater rupture force in CaCl2 (5931.96 kJ mol-1 nm-1) than in NaCl (4662.51 kJ mol-1 nm-1). These results suggest that α6β4 dimerizes more readily than α6β1, and that their binding affinities change in different ion environments.
BCB-04

A TRIPHASIC LOOP-MEDIATED ISOTHERMAL AMPLIFICATION PRIMER DESIGN AND VALIDATION WORKFLOW FOR THE DETECTION OF A HETEROGENOUS TARGET: blaOXA-51-like GENE

Mark B. Carascal, Joy Ann P. Santos, Windell L. Rivera, and Raul V. Destura
ABSTRACT

​Introduction: Loop-mediated isothermal amplification (LAMP) primer designing for heterogenous gene targets are currently not straightforward nor established. In this study, we proposed a three-phase workflow for the design and in silico validation of primers for blaOXA-51-like gene, a beta-lactamase gene known to have many gene variants. 

Objectives: Our goal is to propose and validate a workflow consisting of: (1) pre-design phase which involves multiple sequence alignment of the variants of the target genes, and determination of input sequence for the primer design program; (2) the design phase which involves the actual parameter setting and primer designing using the input sequence from the previous phase; and (3) the in silico validation phase which involves an initial nucleotide search for primer sequence identity, and target-binding efficiency testing of the designed primers from a pool of reference sequences using electronic LAMP. 

Major Findings: Following the workflow, we designed and picked the best primer set for our target based on the screening of primer characteristics. Our electronic LAMP analysis revealed that the designed primers can amplify 87-100% of the different variants of the blaOXA-51-like genes. To provide an initial validation of the in silico results, we also performed experimental LAMP assay using the designed primers to detect blaOXA-51-like gene variants from actual DNA samples with sequence-confirmed target. Our LAMP experiment revealed that the primer set amplified the genes from all of our samples. Our study provides initial evidence that a triphasic LAMP primer design workflow is useful for LAMP targeting heterogenous genes. 

Implications: We hope that our proposed triphasic workflow for LAMP primer design and validation can be used by LAMP technologists in designing their own primers for heterogenous gene targets for various applications.

Keyword: blaOXA-51-like, eLAMP, in silico, LAMP, primer design
BCB-05

CONCERTED VIRTUAL SCREENING OF MYXOBACTERIAL NATURAL PRODUCTS REVEAL DUAL INHIBITORS OF SARS-COV-2 SPIKE PROTEINS

Rey Arturo T. Fernandez, Mark Tristan J. Quimque, Kin Israel R. Notarte, Joe Anthony H. Manzano, Delfin Yñigo H. Pilapil, John Jeric P. San Jose, Omar A. Villalobos, Von de Leon and Allan Patrick G. Macabeo
ABSTRACT

The coronavirus disease 2019 (COVID-19) is a major public health concern caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted to a pandemic causing more than fifty million cases including approximately eight-thousand Filipino mortalities. In this study, we exploited the potential of secondary metabolites from Myxobacteria – a known producer of structurally and functionally diverse metabolites with broad-spectrum antiviral activity. Thus, the inhibitory prospects of 74 antiviral Myxobacterial secondary metabolites were assessed through in silico molecular interaction-based approaches against mechanisms underlying SARS-CoV-2 viral entry. Ligands were prepared using Avogadro and the three-dimensional structures of the proteins were derived from RCSB PDB. Virtual screening of the prepared library was performed following the Broyden-Fletcher-Goldfarb-Shanoo algorithm of AutoDock Vina and binding affinity of the enzyme–ligand complex conformation was determined using UCSF Chimera, visualized and analyzed using BIOVIA Discovery Studios. The 74 secondary metabolites were docked against the receptor binding domains (RBDs) of the SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2) and glucose-regulated protein 78 (GRP78). Molecular dynamics simulations of the spike protein complex of SARS-CoV-2 was studied in YASARA dynamics software package with the aid of AMBER14 force field. SwissADME software and OSIRIS property explorer program were also used to predict in silico the pharmacokinetic and toxicity profile of the compounds, respectively. Among the metabolites screened, the chondramide group of metabolites – chondramide C3 and chondramide C9 – showed highest affinity to ACE2 (-8.6 kcal/mol) and GRP78 (-8.9 kcal/mol) RBD of the viral spike, respectively. Protein-protein docking experiments also showed repulsive interactions of inhibitor-spike protein complex with ACE2 and GRP78 receptors. Selectivity of chondramide C3 towards the ACE2 RBD of the spike was demonstrated by docking the ligand to ACE2 receptor itself. When the binding energies (BEs) of chondramide C3 towards ACE2 RBD (-8.6 kcal/mol) and ACE2 receptor (-7.6 kcal/mol) were compared, it displayed a stronger affinity towards the spike protein. The top fifteen strong binding Myxobacterial secondary metabolites were also docked against SARS-CoV-2 mutants A475V, L452R, V483A, and F490L wherein chondramide A9 consistently demonstrated high affinity towards each variant with a BE of -9.1 kcal/mol. These variants of the RBD of spike to ACE2 exhibit resistance to neutralizing antibodies. The secondary metabolites were also screened to the globally prevalent mutation D614G of the spike protein with a co-occurring mutation, I472V, at the RBD of ACE2. Chondramide C emerged with the strongest BE towards the D614G-I472V variant at -8.5 kcal/mol. Molecular dynamics simulations demonstrated stability of chondramides C, C3 and C9 when complexed with their target RBDs of the viral spike in a 120ns simulation. Finally, the top ligands were predicted to confer favorable pharmacokinetic and toxicity properties. Thus, Myxobacterial chondramides are promising compounds to develop drugs against SARS-COV-2 entry.

Keywords: SARS-CoV-2, spike proteins, Myxobacterial secondary metabolites, molecular docking ​
BCB-06

MOLECULAR AND IN SILICO STRUCTURAL CHARACTERIZATION OF VIRAL GENOME- LINKED PROTEIN (VPg) OF THE BANANA BRACT MOSAIC VIRUS INFECTING ABACA

Leny C. Galvez, Rhosener Bhea L. Koh, Catherine Joyce B. Brillantes and Vermando M. Aquino
ABSTRACT

Abaca is an important agricultural crop in the Philippines due to the high commercial value of its fibers. The abaca industry; however, is plagued with multiple viral diseases, one of which is the banana bract mosaic virus (BBrMV). The viral protein genome-linked (VPg), one of the protein components of the BBrMV genome, is known to play significant roles in the potyviral life cycle. VPg interaction with the host eukaryotic translation initiation factor 4E (eIF4E) is required for successful potyviral infection. The study aimed to clone and characterize BBrMV VPg and determine the structural and protein-protein binding properties through in silico analysis. The full coding sequence of BBrMV VPg was isolated from BBrMV-infected abaca, expressed in E. coli and analysed through in silico docking analysis with predicted eIF4E proteins of abaca. SDS-PAGE analysis showed a 27 kDa protein corresponding to 6xHis-tagged BBrMV VPg which was confirmed by immunoblot analysis with anti-6xHis antibody. The protein was found both in the soluble and insoluble fraction.  Homology modelling through the I-TASSER server showed BBrMV VPg had high structural similarity with the potato virus Y (PVY) VPg. Protein docking analysis between the BBrMV VPg and three putative abaca eIF4E structures via HADDOCK showed the docking of the loop α2-α3 region of BBrMV VPg to the cap binding pocket of MteIF4E which has been previously observed for PVY VPg-eIF4E interaction. Binding affinity values and dissociation constants derived from PRODIGY analysis showed the high binding affinity between BBrMV VPg and the three abaca eIF4Es. The predicted dimeric BBrMV VPg structure showed the interface to be at the loop β4-β5 region which suggests multiple functionality of BBrMV VPg. These findings will be significant for further elucidating the mechanism of virus-host interaction specifically in BBrMV and abaca. 

Keywords: potyvirus, VPg, recombinant protein expression, immunoblot, homology modelling, protein-protein interaction
BCB-07

IN SILICO CHARACTERIZATION OF GSPXII: A NOVEL GAMMA-CONOTOXIN-LIKE TURRITOXIN TARGETING THE CARDIAC PACEMAKER CHANNEL

Marian Gayle Angela C. Guevara, Neil Andrew D. Bascos, and Cynthia P. Saloma
ABSTRACT

Turritoxins are venomous peptides from the Family Turridae. Gene mining performed within our laboratory revealed that Gemmula speciosa has conotoxin-like and non-conotoxin-like peptides that may similarly target ion channels and receptors with high specificity similar to that of the Conus peptides which have been harnessed for use in pharmacology. One of the peptides from this study was GspXII, a 46 AA turritoxin that shares the γ-conotoxin framework XII present among published γ-conotoxins and γ-conotoxin-like peptides based on multiple sequence alignment. γ-conotoxins target the pacemaker channels; however, none of these have elicited a phenotype in vertebrate models. The intravenous and intracranial injection of GspXII in mouse models resulted in a decrease in heart rate and back stiffening. Based on previous experiments, GspXII may target the cardiac pacemaker channel, HCN4.  To test this hypothesis, in silico based docking studies were done using structural models of the peptide, and the target receptor (HCN4).  Structures of the GspXII peptide were modelled through I-TASSER (zhanglab.ccmb.med.umich.edu/I-TASSER/) with and without disulfide constraints predicted by DiANNA (clavius.bc.edu/~clotelab/DiANNA/). These models, together with the prototype of the γ-family of conotoxins, PnVIIA, were used to dock to HCN4 (PDB ID: 6GYO, 6GYN) via ClusPro 2.0 (cluspro.bu.edu/). GspXII was observed to target HCN4 in both hyperpolarized and cAMP-bound states.  The predicted binding of GspXII to the HCN4 pore is expected to prevent the flow of ions through the channel. Notably, PnVIIA was not observed to dock onto the pore of the HCN4 channel; hence, this data supports that PnVIIA is unable to elicit a phenotype in vertebrates (Fainzilber et al., 1998). GspXII was also not observed to dock to the pore of the HCN1 channel (PDB ID: 5U6O, 5U6P, 6UQF) despite the similarity of HCN4 and HCN1, suggesting a specific GspXII-HCN4 interaction. GspXII remains as the only member of the γ-conotoxin family of peptides that elicits a phenotype in vertebrate models.  Our results suggest this mechanism involves the specific targeting of the HCN4 channel by this pore-blocking peptide. 

Keywords: Turritoxin, Ion Channels, Molecular Docking
BCB-08

DESIGNING A MULTI-EPITOPE VACCINE USING EPITOPES FROM THE STRUCTURAL PROTEINS OF SARS-COV-2: AN IMMUNOINFORMATICS APPROACH

Leana Rich M. Herrera
ABSTRACT

The rapid transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted to hundreds of thousands of deaths worldwide. It has severely affected the economy and the healthcare system in many countries, making it crucial to accelerate vaccine development against SARS-CoV-2. Thus, this work utilized immunoinformatics in designing a novel multi-epitope vaccine that can potentially induce immune response through mapped epitopes from immunogenic, and abundantly expressed structural proteins in SARS-CoV-2. 
Epitopes were screened and evaluated using various immunoinformatics tools and databases. Antigenicity, allergenicity, and population coverage were assessed. Epitopes were adjoined to form a single vaccine construct (Cvax), linked with 50S ribosomal protein as an adjuvant. Physicochemical properties, cross-reactivity, antigenicity, and allergenicity of Cvax were evaluated. The tertiary structure of Cvax was modelled, refined, and validated for docking with toll-like receptor 4 (TLR4). The binding affinity of Cvax-TLR4 was estimated and compared with TLR4-adjuvant as control. Lastly, the immune response with Cvax was simulated, and compared with adjuvant alone. 
Total of 33 epitopes from S (21), E (3), M (5), and N (4) proteins were merged in Cvax. These include epitopes on the receptor-binding motif (RBM) of S protein known to be essential in viral attachment. In silico evaluations classified Cvax as stable, antigenic, and non-allergenic. Epitopes were estimated to have large worldwide population coverage, especially in areas with high infection rates, indicating broader efficacy of Cvax as a vaccine for the most affected populations. Results in this work showed that Cvax can bind to TLR4, indicating immunogenicity, and superior properties necessary for a successful vaccine.
Overall, this work efficiently minimized time, efforts, and cost in urgently designing a vaccine against SARS-CoV-2. In vitro and in vivo studies on Cvax are anticipated.

Keywords: Epitopes, immunoinformatics, in silico, receptor-binding motif, SARS-CoV-2, vaccin
BCB-09

BIOINFORMATIC ANALYSIS OF REPORTED SOMATICALLY MUTATED GENES OF ADENOID CYSTIC CARCINOMA OF THE BREAST: GENE ONTOLOGY AND PROTEIN-PROTEIN INTERACTIONS

Allan L. Hilario, Regina Marie Jastiva, Jose B. Nevado, Jr., John Robert C. Medina, Catherine Lynn T. Silao
ABSTRACT

Background: While adenoid cystic carcinoma of the breast (ACCb) is a rare triple-negative breast cancer with favorable biological behavior, good prognosis and seldom undergo metastasis, its treatment is based on the therapy of triple-negative breast cancer, which is composed of aggressive surgery and highly toxic adjuvant chemo- and radiotherapies. But due to its indolent clinical course, ACCb could be treated with less aggressive surgery and adjuvant therapy. The use of molecular markers with histopathology can be used to arrive at a correct diagnosis to help in the prognostication and treatment. Thus, researches on biomarkers in ACCb are very important in our understanding of this clinical enigma.
 
Objectives: This study was done to determine potential biomarkers for ACCb based on the analysis of curated data generated from a systematic literature review and subjected the generated gene set to enrichment using Gene Ontology (GO) and protein-protein interactions using STRING to further elucidate its cancer biology. 
 
Major Findings: Analysis of 36 somatically mutated genes reported in the literature to have somatic mutation in ACCb using Panther tool, reveals an enrichment of specific groups related by Gene Ontology (GO).  These genes were observed to be involved in  cell biosynthesis, metabolism, and cell proliferation (GO terms: 009889; 000983; 0031325; 0005515; 0005515).    In addition, functional protein-protein interaction analysis also revealed linkages between fusion gene, MYBLI-NFIB, and NOTCH gene in STRING. NOTCH signaling seems to play a central role in tumorigenesis. Overall, the genes were involved in cell proliferation and evasion of apoptosis. However, genes involved in tumor suppression and in counter regulation for  epithelial-mesenchymal transition are responsible for the favorable biology and less metastatic potential of ACCb. 
 
Conclusion/Implications: This report provides a consolidated list of related gene families to identify potential targets for determining biomarkers for more effective ACCb prognostication and management.

Keywords: Adenoid cystic carcinoma, breast, biomarkers, bioinformatic analysis
BCB-10

STRUCTURAL AND MOLECULAR DOCKING ANALYSIS OF GIBBERELLIN INSENSITIVE DWARF1 (GID1) RECEPTORS OF ABACA

Rhosener Bhea L. Koh and Vermando M. Aquino
ABSTRACT

The abaca is an economically important fiber crop; however, knowledge on the molecular mechanisms behind fiber development is limited. Gibberellins or gibberellic acids (GA) are plant growth regulators known to regulate fiber cell development in various fiber crops. GA perception in land plants is mediated by the GA receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1). GA binds to GID1 via the GA binding pocket and activates the GA-response pathway through the association of the GA-GID1 complex with the DELLA inhibitor protein. The degradation of the DELLA protein activates the transcription of GA-response genes. Recently, three abaca GID1 (MtGID1) genes were cloned and sequence analysis revealed them to be GA receptors. The study therefore aims to predict the 3D protein structures of the three MtGID1 proteins (MtGID1-1, MtGID1-2 and MtGID1-3) through homology modelling and to conduct protein docking analysis with DELLA protein and GA ligands. Homology modelling revealed the top structural analogs to be Arabidopsis thaliana GID1 (AtGID1a) receptor with the conservation of GID1 core domain structure and N-terminal extension lid structure. Superimposing the three MtGID1 structures showed the location of the loop variable region that connects the N-terminal lid to the GID1 core domain with MtGID1-3 having the shortest loop region among the MtGID1 proteins. Docking of MtGID1 proteins with AtDELLA showed interaction of the N-terminal lid of the three MtGID1 proteins to the DELLA motifs and resulted in negative binding affinity values indicating spontaneous formation the MtGID1-AtDELLA complex. Protein-ligand docking analysis of MtGID1 proteins with bioactive GA molecules showed the residues that are canonically determined to be involved in GA-binding pocket and N-terminal lid closure. These findings suggests that the identified GID1 proteins are bona fide GA receptors of abaca and are capable of activating the GA-GID1-DELLA signaling pathway in abaca.

Keywords: Musa textilis, gibberellin receptor, homology modeling, protein-protein docking, protein-ligand dockin
BCB-11

MODEL PREDICTION AND MOLECULAR DOCKING SIMULATIONS OF A NOVEL CONE SNAIL TOXIN, TCON-1

A.P. Limpot, N.A.D. Bascos, and C.P. Saloma
ABSTRACT

Venom from terrestrial and aquatic animals has always been a source of fear for mankind, but studies have shown that this cocktail of toxins is a rich source of potential pharmacological molecules. Predatory marine snails are known to harbor potent toxins in their venom that elicit an array of physiological phenomena, one of which has already been developed into a commercial analgesic. A novel cone snail toxin, tcon-1, was discovered through the transcriptomic analysis of three marine snails (C. cerithina, U. bisaya, and G. speciosa) and was subsequently characterized in silico and expressed in vitro. The initial in silico analysis revealed that tcon-1 is a structural analog of a previously described Conus striatus toxin called con-ikot-ikot. In this study, a protein model of tcon-1 was predicted by I-TASSER and subsequently docked unto the con-ikot-ikot target receptor. A dimerized model of tcon-1 was utilized in the molecular docking simulations against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) using ClusPro. The docking results show that tcon-1 binds to similar regions as con-ikot-ikot in its putative target receptor, the AMPAR. Succeeding in vitro experiments relating to these observed similarities will shed light on the validity of the predicted functional mechanism of tcon-1 action. 

Keywords: Molecular docking, Protein modeling, Turritoxin
BCB-12

THE POSSIBLE ROLE OF SELECTED ANTIDEPRESSANT METABOLITES IN ANTITUMOR IMMUNITY: A MOLECULAR DOCKING STUDY OF GRANZYME B

John Raphiel C. Macatangay, Wynnevania Kirsten C. Ramos, Shella Mae G. Real, and Tabitha L. Amora
ABSTRACT

Medical researches on cancer treatment and prevention have been on the highest demand for many years. Many patients who undergo such treatments also suffer from clinical depression. The role of secondary metabolites on tumor growth and depression may open up a spectrum of possibilities in the development for an effective treatment against cancer.
 
Secondary metabolites including alkaloids, phenolic acids, and terpenes with antidepressant property were examined for their potential role in antitumor immunity. To determine their possible role in antitumor immunity, a molecular docking study was performed on twelve selected antidepressant metabolites with Granzyme B by using the Autodock Vina software. Parameters such as the binding affinity, bond distance, as well as amino acid interactions, were measured.
 
Results showed that chlorogenic acid had the highest binding affinity among the 12 selected antidepressant metabolites, while mauritine A displayed the highest number of interactions with the active site of the enzyme. Gallic acid showed the shortest bond distance with the enzyme. 
 
The study suggests that chlorogenic acid, mauritine A and gallic acid have the highest possibility among the selected secondary metabolites of exhibiting antitumor immunity with antidepressant effects which may help in the oncologic treatment of cancer patients who also suffer clinical depression. Further study is encouraged involving other parameters, other classes of secondary metabolites, the compounds’ mechanisms of action, and in vivo researches.

Keywords: Granzyme B, molecular docking, antidepressant metabolites, antitumor immunit