02. Yuliana.cdr Vol.14, No.2, June 2020, p 52-65 DOI: 10.5454/mi.14.2.2 In Silico Study on Testing Antidiabetic Compounds Candidate from Azaphilone Monascus sp. 1 1 1 ANNA YULIANA , HILMAN FITRIAJI S P , KHOFI SITI MUKHAUFILLAH , AND LINA 2 RAHMAWATI RIZKULOH 1 Department of Pharmacy, STIKes Bakti Tunas Husada, Jl.Cilolohan No.36,Tasikmalaya 46184, Indonesia; 2 Department of Pharmacy, Universitas Perjuangan, Jl. Pembela Tanah Air (PETA) No. 177, Tasikmalaya 46115, Indonesia. Monascus sp. can be used as an ingredient in rice fermentation to produce red rice, called Angkak. In Asia, Angkak is used as traditional medicine and food containing bioactive compounds, one of which is monakolin that has the potential to be a nutraceutical. Monascus sp. produces five main pigments: red (monascorubramin, rubropunktamin), orange (monascorubrin, rubropunktatin), and yellow (monaskin, ankaflavin) which have biological activity. In subsequent developments, many new pigments were found which derivatives of the main pigments Monascus sp. are, but information regarding their biological effects is still very limited. The purpose of this study was to determine the pigment derivative compounds of Monascus sp. as a candidate compound for antidiabetic drugs. This study used 57 pigment derivative compounds Monascus sp. which is done In silico. 2GPA protein (Glycogen Phosphorylase) is used as an antidiabetic receptor. The software used in this research includes ChemDraw, Marvin Sketch, Molegro Molecular Viewer, Biovia Discovery Studio, and Autodock. The ADME study was conducted using PreADMET web-based software. The results of the drug scan test on the MPs4 isolate compound have a value that meets the requirements in all parameters such as molecular weight, proton donor, proton acceptor, Log p and molar refractory. The ADME test results on the MPs4 Isolate compound have a value that meets the requirements in all parameters of Caco2, HIA (Human Intestinal Absorption), and in PPB (Protein Plasma Binding). The results of the docking, the Isolate MPs4 compound are the best compounds and meet the requirements because they have smaller binding affinity than natural ligands and comparison ligands (Glibenclamide). The results of this study, MPs4 isolate can be used as a candidate for new antidiabetic drugs, but still requires further research, including In vitro and In vivo tests. Key words: antidiabetic, azaphilone, docking, in silico, Monascus sp. Monascus sp. dapat digunakan sebagai bahan fermentasi beras sehingga menghasilkan beras berwarna merah yang disebut Angkak. Di Asia, Angkak digunakan sebagai pengobatan tradisional dan juga makanan yang mengandung senyawa bioaktif, salah satunya adalah monakolin yang berpotensi sebagai nutraceutical. Monascus sp.menghasilkan pigmen utama yaitu merah (monaskorubramin, rubropunktamin,), orange (monaskorubrin, rubropunktatin), dan kuning (monaskin, ankaflavin) yang memiliki aktivitas biologis. Pada perkembangan berikutnya, ditemukan banyak pigmen baru yang merupakan turunan dari pigmen utama Monascus sp., tetapi informasi mengenai efek biologisnya masih sangat terbatas. Tujuan penelitian ini adalah untuk mengetahui senyawa turunan pigmen Monascus sp. sebagai senyawa kandidat antidiabetes. Penelitian ini menggunakan 57 Senyawa Turunan pigmen Monascus sp. secara In silico. Sebagai reseptor antidiabetes digunakan protein 2GPA(Glikogen Fosforilase). Perangkat lunak yang digunakan dalam penelitian ini meliputi ChemDraw, Marvin Sketch, Molegro Molecular Viewer, Biovia Discovery Studio, danAutodock. Studi ADME dilakukan dengan software berbasis web PreADMET. Hasil uji drug scanmenunjukkan senyawa Isolate MPs4 memiliki nilai yang memenuhi syarat dalam semua parameter seperti berat molekul, donor proton, akseptor proton, Log p dan refractory molar. Hasil uji ADME pada senyawa Isolate MPs4 memiliki nilai yang memenuhi syarat dalam semua parameter Caco2, HIA (Human Intestinal Absorption), maupun pada PPB (Protein Plasma Binding). Hasil uji docking menunjukkan senyawa Isolate MPs4 menjadi senyawa yang terbaik dan memenuhi syarat karena memiliki binding affinity lebih kecil daripada ligan alami dan ligan pembanding (Glibenklamid). Hasil dari penelitian ini, Isolate MPs4 dapat dijadikan salah satu kandidat obat baru antidiabetes, namun masih memerlukan penelitian lebih lanjut diantaranya uji In vitro dan In vivo. Kata kunci: bakteri pelarut fosfat, fosfor, kultur murni dan campuran, pertanian, tanah MICROBIOLOGY INDONESIA Available online at http://jurnal.permi.or.id/index.php/mionline ISSN 1978-3477, eISSN 2087-8575 *Corresponding author: Phone: +62-265-334740; Fax: +62- 265-334745; Email: anna_yuliana@stikes-bth.ac.id hyperglycemia, protein, and fat related to a lack of insulin secretion. Polyuria, polydipsia, weight loss, tingling, polyphagia are symptoms that are felt by people with Diabetes Mellitus (Fatimah 2015). The mechanism of DM type 2 is a decrease in Diabetes mellitus is a disease that characterized by disruption of carbohydrate metabolism and insulin sensitivity (insulin resistance) and failure of pancreatic beta cell function which results in decreased production of insulin that cause hyperglycemia (Perkeni 2015). Monascus sp.can be used as rice fermentation material to make red rice, called Angkak. In Asia, Angkak is used as traditional medicine and food, contains bioactive compounds. One of them is a monacolin compound, which has potential as a nutraceutical (Nguyen et al. 2017). Research on Monascus sp. pigments is growing rapidly, including the discovery of new pigments, which are derived from the main pigments: yellow, orange and red. The research data obtained is still a separate data from any research journals, so that complete data are needed, particularly information regarding biological activity. From the six major pigments, 57 derivatives have been found until now. (Yuliana et al. 2017). As seen from Table 1, some pigments derived from Monascus sp. include red (monascorubramin, r u b r o p u n k t a m i n ) , o r a n g e ( m o n a s c o r u b r i n , rubropunctatus), and yellow (monaskin, ankaflavin) which have biological activity. Monascus sp. pigments widely used as a food coloring and flavoring in the food industry, especially for fish such as fish paste, surimi and meat products such as sausages and ham. In addition, this pigment can be used not only in the food sector, but also in the cosmetic and pharmaceutical industries (Seyedin et al. 2015). Pigments that have the potential to reduce blood Table 1 The main pigments structure of Monascus sp. (Yuliana et al. 2017) Volume 14, 2020 Microbiol Indones 53 54 YULIANA ET AL. Microbiol Indones glucose levels are rubropunctamine (red) and rubropunctatine (orange) pigments (Sulistyaning 2013). The purpose of this study was to determine the pigment derivative compounds of Monascus sp. as a candidate compound for antidiabetic drugswith In Silico test. MATERIALS AND METHODS The tools used in this study are personal computers with processor specifications: Intel CORE i7, 4.0 GB RAM; 64 bit Operating System, Operating System: Windows 10 Pro. The software used is Marvin Sketch version 5.2.5.1, Molegro Molecular Viewer (MMV) version 2.5,ChemdrawUltra, Biovia Discovery Studio 2017, Autodock, and web programs such as PreADMET, PRODRG2, Pharm Mapper and PDBsum. All software is open source. The materials in this study include the receptors that have been identified, downloaded from protein data bank (PDB) and 57 dyestuff compounds isolated from azaphilone derivatives from Monascus sp. Ligand Preparation. Ligands were drawn using ChemDraw software and then optimized by protonation at 7.4 pH at Marvin Sketch (Ruswanto et al. 2014). The procedure is performed on Azaphilone- derived ligands and then stored in the mol2 format. Optimization of the structure aims to see the conformation of molecules and see the low potential energy that has been adjusted based on pH conditions in the body. Drug Scan. Drug observation was carried out on dyestuff compounds derived from Monascus sp.by considering Lipinski's rule of five as well as oral and ligand bioavailability. The parameters used were<500 g / mol molecular weight, <5hydrogen bond donors, <10 hydrogen bond acceptors, and 40-130 molar refractory.These parameters can be determined with the help of Marvin Sketch software (Ruswanto 2015). Receptor Preparation. There are 5 enzyme structures (receptors) for antidiabetic: 1C8L (Glicogen Phosporilase A), 1H5U (Glicogen Phosporilase B), 2FW3 (Karnitin Palmitoyltranspherase 2), 2QMJ (Maltase Glucoamilase), and 2GPA (Glicogen Phosporilase). Pdb format is created after the codes 1C8L, 1H5U, 2FW3, 2QMJ, 2GPA are downloaded from PDB (Protein Data Bank). Then it is prepared to separate from its natural ligand, adding hydrogen and removing solvent molecules (Ruswanto et al. 2018). ADMET Study. ADMET compounds Profiling is done by applying the ADMET descriptor algorithm and the ADMESTAR database that freely available at (http://admetexp.org) (Qidwai 2017). Docking Method Validation. Before the compound docking process is carried out with protein, the docking method is validated using Autodock 4.2.6. to see the Root Mean Square Deviation (RMSD)as docking validityparameters (Lelita et al. 2017). Validation was done by using natural ligand re- docking on each receptor were used. Re-docking is the process of separating the natural ligand crystal structure docking receptor then carried back to the receptor. The docking parameter is valid if the RMSD value from the redocking results is ≤ 2.0 Å (Sherman et al. 2006). The value of RMSD indicate acceptable accuracy, whereby if the value of RMSD <2 Å means indicates that the smaller the error of the docking results, so it can be said to be valid ( ).Lelita et al. 2017 Molecular Tethering. Test compounds and proteins downloaded from PDB were prepared with Autodock 4.2.6, before the tethering process, the parameters, dimensions, and the coordinates of the grid box were adjusted. The dimensions of the grid box are adjusted to the size of each ligand, while the coordinates of the grid box are adjusted based on the coordinates of the center of its natural ligand. Before that, the location of the gridboxwas determined using the Autodock program Tools. Grid Box is the location of the ligand mooring space which will be docking and have settingsincludes center_x, center_y, and center_z. To determine the size of a grid box is setby using spacing (armstrong). The placement of the Gridboxis based on the location of the test ligand and the active side of the protein.The grid box used is X = 31,864, Y = 21,182, and Z = 26,477.The parameter used is the calculation of 100 times runs GA (genetic algorithm). Compounds for testing and prepared proteins are put together in one folder for further gridding and docking (Yuliana et al. 2019). RESULTS Drug Scan. On the results of the drugscan test on Azaphilone derivatives in Table 2, shows that not all azaphilone derivatives fulfill the Lipinski's Rule of Five parameters requirements. Such as Glycyl Rubropuntatin, Isolate MPs3, Isolate MPs2, Isolate M P s 1 , N - g l u t a r y l M o n a s c u r o b a m i n e , N - Table 2 Drug scan test result No Name of Compound Drug Scan M olecular weight Proton Donor Proton Acceptor Log P Refractory M olar < 500 g/mol < 5 < 10 < 5 40-130 1 Glycyl Rubropunctatin 413.470 1 11 3,33 114,09 2 Isolate MPs4 439.552 1 9 4,32 126,87 3 Isolate MPs3 439.508 1 11 4,08 123,54 4 Isolate MPs2 538.645 5 14 3,74 161,46 5 Isolate MPs1 510.591 5 14 2,85 152,26 6 N-glutaryl Monascurobamine 511.571 2 15 4,30 138,82 7 N-glutaryl Rubropunctamine 483.517 2 15 3,41 129,62 8 PP-V 412.461 3 10 3,26 125,22 9 N-glycosyl rubropunctamine 557.640 4 17 2,65 149,92 10 N-glycosyl monascurobamine 585.694 4 17 3,54 159,12 11 Compound R3 374.433 1 10 2,05 101,41 12 Red Derivat 1 453.535 1 11 4,65 128,03 13 Red Derivat 2 425.481 1 11 3,76 118,83 14 Red Derivat 3 497.544 2 15 4,01 134,07 15 Red Derivat 4 469.490 2 15 3,12 124,87 16 Red Derivat 5 453.535 1 11 4,65 128,03 17 Red Derivat 6 425.481 1 11 3,76 118,83 18 Red Derivat 7 497.544 2 15 4,01 134,07 19 Red Derivat 8 469.490 2 15 3,12 124,87 20 Un Named 375.465 3 9 1,16 103,91 21 Monascopyridine A 355.434 0 7 4,23 98,81 22 Monascopyridine B 383.488 0 7 5,12 108,01 23 Monascopyridine C 357.450 1 9 3,90 99,88 24 Monascopyridine D 343.467 1 7 4,61 100,56 25 New Red Pigmen 375.465 3 9 1,16 103,91 26 Monascuskaodione A 356.418 0 8 3,36 100,67 27 Monascuskaodione B 384.472 0 8 4,27 109,87 28 Red Shandong 1 303.402 4 7 0,54 91,77 29 Red Shandong 2 331.456 4 7 1,43 100,98 30 Monankarin A-B 358.3851 2 8 2.38 98,10 31 Monankarin C-D 372.4117 2 7 2.90 103.14 32 Monankarin E 358.3851 2 7 2.53 98.67 33 Monankarin F 356.4123 2 6 2.99 103.21 34 Monascusone A 254.2790 3 6 -0.99 67.08 35 Monascune B 302.3218 0 7 1.64 82.07 36 FK 17-P2B2 236.2637 2 5 0.35 66.34 37 Xantomonascin A 388.4111 2 8 4.00 102.20 38 Xantomonascin B 414.4914 2 8 3.76 126.81 39 Y3 448.571 6 8 0.34 115.88 40 Monapurones A 330.4180 1 6 2.98 97.87 41 Monapurones B 344.4446 0 5 3.93 101.83 42 Monapurones C 344.4446 0 5 3.93 101.83 43 Monaphilones A 374.5137 1 6 4.61 111.50 44 Monaphilones B 332.4339 1 6 3.27 97.70 45 Monaphilones C 336.4657 1 7 4.14 95.95 46 Monashexenone 320.4232 1 7 3.70 92.33 47 Rubropuctin 358.4712 1 6 4.02 107.15 48 Monarubrin (Y,BF) 330.4180 1 6 3.13 97.95 49 Yellow II 372.4547 1 7 4.31 116.32 50 Purpureus one 390.5131 0 8 5.43 107.95 51 Monascuspiloin 360.4440 1 6 3.11 101.32 52 Monaphilol A 384.4654 1 6 3.62 111.10 53 Monaphilol B 356.4123 1 6 2.73 101.89 54 Monaphilol C 440.5287 1 8 3.59 125.32 55 Monaphilol D 412.4755 1 8 2.70 116.12 56 Monasfluor A 354.4394 0 5 3.98 104.30 57 Monasfluor B 384.4654 0 7 4.27 109.87 Volume 14, 2020 Microbiol Indones 55 g l u t a r y l r u b r o p u n c t a m i n e , N - g l y c o s y l r u b r o - punctamine, N-glycosylmonascurobamine, Red Derivat 1, Red Derivat 2, Red Derivat 3, Red Derivat 4, Red Derivat 5, Red Derivat 6, Red Derivat 7, Red Derivat 8, Monascopyridine B, Y3, Purpureus one, while the Azaphilone derivative compounds that fulfill Lipinski's rules are Isolate MPs4, PP-V, Compound R3, Un Named, Monascopyridine A, Monascopyridine C, M o n a s c o p y r i d i n e D , N e w R e d P i g m e n t , Monascuskaodione A, Monascuskaodione B, Red Shandong 1, Red Shandong 2, Monankarin C-D, Monankarin A-B, Monankarin E, Monankarin F, FK 17-P2B2, Monascusone A, Monascusone B, Monasfluor A, Monasfluor B, Xantomonascin A, Xantomonascin B, Monapurones A, Monapurones B, Monapurones C, Monaphilol D, Monaphilol A, Monaphilol B, Monaphilol C, Monaphilones B, Monaphilones A, Monaphilones C, Monashexenone, Rubropuctin, Monarubrin (Y,BF), Yellow II, Monascuspiloin, so that it can be used as a candidate for drug compounds for further testing. Receptor Preparation. There are 5 enzyme structures (receptors) for antidiabetic, which is 1C8L, 1H5U, 2FW3, 2QMJ, 2GPA. To separate them from the original ligand, the addition of hydrogen and the removal of solvent moleculesare needed. Then the enzymes / receptors that have been downloaded and stored in the form of PDB were analyzed using PDBSum. Figure 1 showed that the 2GPA receptor shows a stable structure because the percentage of residue in the most favored region is 89.7% and in the disallowed region is 0.1%. The quality of the protein structure is considered good if the residue in the disallow region is less than 15% and the amino acid residue in the most favored region is greater than 50%. The greater percentage of amino acid residues in the most favored and the lower percentage of residues in the disallowed region, the better the quality of the structure. So it can be said that the protein structure of 2GPA receptor has good quality and can be used for further analysis. ADMET Study. Based on ADME test results using web-based PreADMET software in Table 2, Azaphilone derivative compounds have medium permeability values, which are in the range of 4-70%. The process of absorption in the human intestine is in a good range that is in the range of 70-100%. Then for the binding of proteins in the blood compound ; MPs4 Isolate, MPs3 Isolate, Red Derivate 1, Red Derivate 5, Monascopyridine B, Monascopyridine D, Monascuskaodione B, Xantomonascin A, Xantomonascin B, Monaphilones A, Rubropuctin, M o n a s c o p y r i d i n e B , M o n a s c o p y r i d i n e D , M o n a s c u s k a o d i o n e B , X a n t o m o n a s c i n A , Xantomonascin B, Monaphilones A, Rubropuctin, Monarubrin (Y, BF) Yellow, Monaphilol A, Monaphilol B, Monasfluor A, Monasfluor B have a high value of> 90% showing a strong bond with plasma proteins in the body. Docking Method Validation. Validation is done by Autodock 4.2.6. Based on the data from Table 4, the result shows that the 2GPA PDB is valid where the RMSD value has fulfil the ≤2 requirements, which is have value of 0.77. Meanwhile the 1H5U, 2FW3, 1C8L PDB are not valid because the RMSD result shows that the values​​exceed the specified ≤ 2 range. The RMSD results of those three GDP codes are 2.85, 2.03, and 3.41. In the other hand, the 2QMJ PDB still fulfills the requirements, it have value of 1.28, but when the RMSD value of the 2GPA PDB compared with the 2QMJ PDB, it can be confirmed that the RMSD of the 2GPA PDB is smaller, because if the RMSD value is getting smaller, it shows that the position of the ligand is better because it getting near to the original conformation. Molecular Tethering. As can be seen from Figure 2, the receptor used with the docking ligand obtained an RMSD value of <2.0 Å, it shows that it has fulfilled the validity requirements. DISCUSSION A protein structure is declared good if the most favored regions are ≥ 90% and disallowed regions less ≤ 1%. Another parameter used in the selection of receptors is that the RMSD value must be ≤ 2, because if the RMSD value is getting closer to zero then the original ligand with a copy of the ligand is increasingly similar. From these parameters, the enzyme / receptor with the code 2GPA (Glycogen Phosphorylase) fulfills the requirements because it has an RMSD value of 0.77. Caco2 cells are the distribution of drugs through intestinal epithelium that derived from human colon adenocarcinomas that have multiple transport routes. HIA is the result of absorption and bioavailability processes that are evaluated from the amount of expenditure through bile, urine, and feces. PPB (Protein plasma binding) is a part of the drug that is available in a free form for circulation to all tissues in the body (Nursamsiar et al. 2016). Validation of docking is done with water and without water, it is intended to determine the effect of 56 YULIANA ET AL. Microbiol Indones No Name of Compund Caco2 (nm/sec) HIA (Human Intestinal Absorption) % PPB (Protein Plasma Binding) % 1 Glycyl Rubropuntatin 20.9325 Medium 96.702970 Good 87.663371 Weakly Bonded 2 Isolate MPs4 25.6923 Medium 99.303546 Good 92.314035 Strongly Bonded 3 Isolate MPs3 21.5677 Medium 98.309963 Good 90.416630 Strongly Bonded 4 Isolate MPs2 8.92909 Medium 78.193552 Good 78.061242 Weakly Bonded 5 Isolate MPs1 9.25845 Medium 74.407933 Good 64.976138 Weakly Bonded 6 N-glutaryl Monascurobamine 19.8389 Medium 92.538271 Good 90.486415 Strongly Bonded 7 N-glutaryl Rubropuctamine 19.7598 Medium 90.311224 Good 88.136616 Weakly Bonded 8 PP-V 4.01366 Medium 92.923736 Good 86.114618 Weakly Bonded 9 N-glucosyl rubropuctamine 12.4451 Medium 85.412276 Good 65.185992 Weakly Bonded 10 N-glucosyl monascurobamine 12.5306 Medium 87.690078 Good 79.078783 Weakly Bonded 11 Compound R3 17.4163 Medium 95.677133 Good 73.231309 Weakly Bonded 12 Red Derivat 1 22.1952 Medium 98.668455 Good 90.932647 Strongly Bonded 13 Red Derivat 2 21.2765 Medium 97.891289 Good 88.641765 Weakly Bonded 14 Red Derivat 3 20.5128 Medium 91.491229 Good 89.736964 Weakly Bonded 15 Red Derivat 4 20.4423 Medium 88.981951 Good 86.838945 Weakly Bonded 16 Red Derivat 5 22.1952 Medium 98.668455 Good 90.932647 Strongly Bonded 17 Red Derivat 6 21.2765 Medium 97.891289 Good 88.641765 Weakly Bonded 18 Red Derivat 7 20.5128 Medium 91.491229 Good 89.736964 Weakly Bonded 19 Red Derivat 8 20.4423 Medium 88.981951 Good 86.838945 Weakly Bonded 20 Un Named 17.9896 Medium 89.666473 Good 66.572743 Weakly Bonded 21 Monascopyridine A 26.367 Medium 98.750840 Good 91.953695 Strongly Bonded 22 Monascopyridine B 32.7272 Medium 98.912525 Good 93.500167 Strongly Bonded 23 Monascopyridine C 22.7729 Medium 96.648798 Good 89.685299 Weakly Bonded 24 Monascopyridine D 22.9611 Medium 96.270412 Good 97.268350 Strongly Bonded 25 New Red Pigmen 17.9896 Medium 89.666473 Good 66.572743 Weakly Bonded 26 Monascuskaodione A 28.3725 Medium 98.770329 Good 88.897997 Weakly Bonded 27 Monascuskaodione B 36.0846 Medium 98.771155 Good 92.381422 Strongly Bonded 28 Red Shandong 1 13.6843 Medium 85.719545 Good 71.398196 Weakly Bonded 29 Red Shandong 2 14.2523 Medium 87.122330 Good 87.278357 Weakly Bonded 30 Monankarin A-B 21.4435 Medium 93.56731 Good 85.58307 Weakly Bonded 31 Monankarin C-D 21.9971 Medium 93.909198 Good 87.093425 Weakly Bonded 32 Monankarin E 21.4031 Medium 93.567883 Good 84.456494 Weakly Bonded 33 Monankarin F 35.5122 Medium 93.789307 Good 88.543275 Weakly Bonded 34 Monascusone A 19.3778 Medium 78.683369 Good 34.939799 Weakly Bonded 35 Monascune B 22.9891 Medium 97.536574 Good 61.438550 Weakly Bonded Table 3 Test Results of ADME Azaphilone derivatives Volume 14, 2020 Microbiol Indones 57 Table 3 Test Results of ADME Azaphilone derivatives -Continued- No Name of Compund Caco2 (nm/sec) HIA (Human Intestinal Absorption) % PPB (Protein Plasma Binding) % 36 FK 17-P2B2 0.993 Rendah 90.43201 Good 56.07652 Weakly Bonded 37 Xantomonascin A 19.6124 Medium 88.865206 Good 96.842726 Strongly Bonded 38 Xantomonascin B 26.5245 Medium 94.538788 Good 94.764093 Strongly Bonded 39 Y3 19.3732 Medium 50.125685 Medium 67.649190 Weakly Bonded 40 Monapurones A 26.9554 Medium 95.760530 Good 86.135746 Weakly Bonded 41 Monapurones B 44.272 Medium 97.697949 Good 88.300451 Weakly Bonded 42 Monapurones C 44.272 Medium 97.697949 Good 88.300451 Weakly Bonded 43 Monaphilones A 48.8546 Medium 96.052979 Good 94.089855 Strongly Bonded 44 Monaphilones B 40.8229 Medium 96.054536 Good 90.112573 Strongly Bonded 45 Monaphilones C 26.9554 Medium 95.760530 Good 86.135746 Weakly Bonded 46 Monashexenone 22.609 Medium 95.857284 Good 88.158433 Weakly Bonded 47 Rubropuctin 46.2928 Medium 96.050080 Good 95.896405 Strongly Bonded 48 Monarubrin (Y,BF) 40.5147 Medium 96.071613 Good 92.263384 Strongly Bonded 49 Yellow II 34.2219 Medium 96.423561 Medium 91.738989 Strongly Bonded 50 Purpureus one 31.1835 Medium 98.247814 Good 90.721848 Strongly Bonded 51 Monascuspiloin 30.4892 Medium 96.468903 Good 90.306522 Strongly Bonded 52 Monaphilol A 36.7103 Medium 96.501044 Good 95.427557 Strongly Bonded 53 Monaphilol B 29.408 Medium 96.568439 Good 91.926288 Strongly Bonded 54 Monaphilol C 34.038 Medium 97.366571 Good 89.549401 Weakly Bonded 55 Monaphilol D 27.7997 Medium 97.311031 Good 83.639250 Weakly Bonded 56 Monasfluor A 49.808 Medium 97.649968 Good 92.794086 Strongly Bonded 57 Monasfluor B 36.0846 Medium 98.771155 Good 92.381422 Strongly Bonded Information�: Caco-2� : Low <4 ; Medium 4-70 ; High > 70 HIA � : Bad 0-20 % ; Medium 20-70 % ; Good 70-100 % PPB � : Strongly Bonded > 90 % ; Weakly Bonded < 90 % Table 4 Docking validation results RECEPTORS GRID BOX RMSD X Y Z 2GPA 31.864 21.182 26.477 0.77 1H5U 28.47 21.132 31.662 2.85 2QMJ -29.911 7.647 -17.894 1.28 2FW3 23.57 4.509 34.021 2.03 1C8L 27.833 20.552 31.813 3.66 water on the docking process. In validation the presence of water shows physiological conditions in the body, because water will affect the ligand bond to the receptor and also the formation of hydrogen bonds with the receptor, besides this validation can also show the comparison of the position of the original ligand with the comparative ligand against the receptor when they are docked. The RMSD value is a parameter that can be used, because if the RMSD value obtained from the validation results is ≤2, that is mean the result is good. Molecular tethering of pigments from Monascus sp. was carried out on 57 pigment compounds of Monascus sp. with For the results of interaction 2 GPA receptor. and molecular tethering showed in Table 5. There are only 2 pigments that have smaller binding energy valueswhen compared with antidiabetic drugs 58 YULIANA ET AL. Microbiol Indones Fig 1 Visualization results of Ramachandran plot and procheck statistics. Fig 2 Visualization of docking result. Docking ligand (yellow) Natural ligand (green). Fig 3 Visualization of 2D and 3D docking results for Isolate MPs4 compounds 2 GPA receptor. with on the market (Glibenclamide), The value of free energy bonds on Isolate MPs4 refers to the smallest value, because the value is -11.58 kcal / mole which indicates it has the most stable position. Ligands from Glibenclamide produce Asn284, Gly675 hydrogen bonds. This interaction is also found in Isolate MPs4 that shows the affinity of Isolate MPs4 is better than the comparative ligand (Glibenclamide). The visualization of 2D and 3D docking results for Isolate MPs4 compounds 2 GPA receptor with can be seen from Figure 3. The next lowest free energy bond value is the Red Derivate 6. Red Derivate 6 compound has a smaller binding energy when compared to original ligands and comparative ligands (Glibenclamide) so that they have a stable conformation. The bonds that occur in Red Derivatives 6 are hydrogen bonds, namely Asn284 and Gly675 which are also found in original hydrogen ligand and comparative ligand (Glibenclamide) bonds. Therefore, Red Derivate 6 has the potential to become Volume 14, 2020 Microbiol Indones 59 No Compounds Run Binding Affinity kkal/mol HydrogenBond Amino Acid (Residue Contact) 1 Glibenclamide (comparison) 55 -10.48 ASN284 GLY675 ASN282, ALA383, PHE286, PHE285, HIS341, ASP339, THR378, ALA673, HIS377, ASN484, SER674, LEU139, GLY675, THR676, GLU672,GLY135, GLY677, VAL567, ARG569, TYR648, GLY134, LYS574, ASN133, LEU136, LYS568, ASP284, GLU88, ASN284 2 Original Ligand 32 -6.08 LEU136 ASN284 GLU672 SER674 GLY675 ASN484 LEU136, ASN284,GLU672, SER674, GLY675, ASN484, LYS574, TYR573, HIS377, ALA673, THR676, VAL455, LEU139, GLY135 3 Glycyl-rubropunctatine 28 -10.11 THR676 ASN484 HIS377 THR676, ASN484, HIS377, ARG569, TYR648, LYS568, LYS574, ASN678, GLY677, GLU672, GLN665 GLY675, ALA673, SER674, VAL455, LEU139, GLU88, ASN133, GLY137, ASP283, ASN284, LEU136, GLY135, GLY134 4 Isolate MPs4 21 -11.58 GLY677 THR676 HIS377 ASN284 GLY677, THR676, HIS377 ASN284, ARG569, TYR648, LYS574, LYS568, GLN665, GLY675, ASN678, GLU672, ASN484, ALA673, SER674, VAL455, LEU136, GLY137, GLU88, ASN133, ASP283, HIS341, ASN282, ASP339, THR378, GLY134, GLY135, TYR573 5 Isolate MPs3 40 -9.78 TYR537 GLU672 ALA673 HIS377 THR676 GLY677 TYR537, GLU672, ALA673 HIS377, THR676, GLY677, ASP339, ASN284, GLY135, LEU136, THR378, GLU88, ASN133, ASP283, GLY134, ARG569, TYR648, LYS568, LYS574, ASN678, GLY675, ASN484, SER674, VAL455 6 Isolate MPs2 47 -7.45 HIS377 GLU672 GLY675 LYS680 HIS377, GLU672, GLY675, LYS680, THR378, ASP339, ALA383, PHE285, ASP283, ASN282, ASN284, LEU136, ARG569, HIS341, ASN133, VAL567, GLY677, GLY134, TYR648, ARG138, THR676, GLY135, ASN678, GLN665, SER674, TYR573, ALA673, VAL455 7 Isolate MPs1 83 -9.53 GLN665 SER674 GLY677 THR676 GLY675 HIS377 GLN665, SER674, GLY677, THR676, GLY675, HIS377, LYS568, GLU672, TYR573, ALA673, VAL455, HIS341, THR378, ASP339, LEU136, ASN284, ASP283, LEU139, GLY135, GLY134, ARG569, LYS574, TYR648, ASN678, GLY694, ALA695, SER667, ASN696, VAL567 8 N-glutaryl Monascurobamine 52 -9.30 LEU136 ASP283 LEU136, ASP283, LYS574, LYS568, VAL567, GLY677, THR676, LYS680, GLY135, GLU672, ARG138, GLY675, SER674, ALA673, TYR573, HIS377, GLY137, ASN133, ASP339, ASN284, GLY134, PHE285, HIS341, ALA383, ASN282, ARG569, TYR648 9 N-glutaryl Rubropuctamine 18 -9.66 ASP283 LEU136 THR676 ASP283, LEU136, THR676, GLY137, ASN133, ASN282, GLU88, PHE285, ALA383, ASN284, GLY134, ARG569, HIS341, LYS574, TYR648, LYS568, VAL567, GLY677, LYS680, ARG138, GLY675, GLU672, SER674, GLY135, ALA673, TYR573,HIS377 10 PP-V 89 -9.99 LEU136 ASP283 THR676 LEU136, ASP283, THR676, PHE285, PHE286, ASN133, GLY137, HIS341, GLY134, GLY135, LYS574, LYS568, GLN665, GLY675, GLY677, GLU672, SER674, ALA673, VAL455, TYR573, HIS377, ASN284, THR378, GLU88, ASP339, ASN282, ALA383 11 N-glycosyl rubropuctamine 15 +7.08 ASN284 HIS377 ASN484 GLY135 ASN284, HIS377, ASN484, GLY135, HIS341, PHE285, ALA383, LEU384, ASP339, THR378, ALA673, GLU672, VAL455, SER674, GLY675, LYS568, LYS574, VAL567, GLY677, THR676, ARG138, LEU139, ASP283, ASN133, GLU88, ASN282, LEU136 Table 5 The results of docking pigment tests from Monascus sp. with 2 GPA (Glycogen Phosphorylase) receptor 560 YULIANA ET AL. Microbiol Indones Table 5 The results of docking pigment tests from Monascus sp. with 2 GPA (Glycogen Phosphorylase) receptor -Continued- No Compounds Run Binding Affinity kkal/mol HydrogenBond Amino Acid (Residue Contact) 12 N-glycosyl monascurobamine 90 +7.83 ASN484 SER674 HIS377 ASN284 ASN484, SER674, HIS377, ASN284, GLY677, LYS568, LYS574, GLY123, LEU139, GLY134, THR676, ARG569, ASP283, LEU136, ASN133, GLU88, ASN282, HIS341, PHE285, LEU384, THR378, ALA383, ASP339, ALA673, VAL455, GLU6782, GLY675 13 Compound R3 72 -9.90 ASP283 LEU136 HIS377 ASN484 GLY675 GLY677 THR676 ASP283, LEU136, HIS377, ASN484, GLY675, GLY677, THR676, GLU672, GLN665, ASN678, LYS574, GLY135, ASN284, ASN282, ASN133, GLU88, GLY137, GLY134, LEU139, VAL455, ALA673, SER674, LYS568 14 Red Derivat 1 19 -8.80 GLY675 GLU672 HIS377 GLY675, GLU672, HIS377, SER674, TYR573,ALA673,VAL455, LEU139, LEU136, THR378, ASN284, HIS341, ASP339, ALA383, PHE285, GLY135, ARG569, TYR648, GLY134, GLY677, THR676, VAL567, LYS568, LYS574 15 Red Derivat 2 18 -8.86 ASN484 LEU136 GLY137 ASP283 GLY135 THR676 ASN484, LEU136, GLY137, ASP283, GLY135, THR676, GLY675, ALA673, SER674, VAL455, TYR573, GLU672, ASN284, HIS377, ASP339, HIS341, ALA383, THR378, ASN282, GLU88, ASN133, GLY134, ARG569, LYS574, GLY677, LEU139 16 Red Derivat 3 78 -8.09 THR676 GLY677 GLU672 HIS377 THR676, GLY677, GLU672, HIS377, LYS568, GLY675, LYS574, TYR573, SER674, ALA673, VAL455, LEU139, THR378, HIS341, PHE285, ALA383, ASP339, LEU136,ASN284, GLY135, ASP283, GLY134, TYR648, ARG569, ASN133 17 Red Derivat 4 86 -8.51 GLY677 THR676 GLU672 HIS377 GLY677, THR676, GLU672, HIS377, GLY675, SER674, TYR573, ALA673, VAL455, THR378, LEU136, LEU139, ASN284,ASP283, GLY134, ASN133, ARG569, TYR648, LYS568, LYS574, ASN678, GLY135, GLN665 18 Red Derivat 5 57 -10.30 GLY677 THR676 HIS377 GLY677, THR676, HIS377, VAL455, LEU136, THR378, GLY137, ASN133, GLU88, ASN282, ASP283, ASN284, GLY134, GLY135, TYR573, TYR648, ARG569, LYS680, ASN678, LYS568, LYS574, GLY675, GLU672, ASN484, SER674, ALA673 19 Red Derivat 6 100 -10.63 GLY677 THR676 ASN484 HIS377 GLY677, THR676, ASN484, HIS377, LYS680, ASN678, GLY675, LYS568, LYS574, SER674, GLU672, VAL455, ALA673, LEU139, LEU136, ASP283, GLY137, ASN284, GLY135, GLU88, ASN133, GLY134, TYR648, ARG569 20 Red Derivat 7 2 -9.86 GLY677 ASN484 HIS377 ASN284 GLY677, ASN484, HIS377, ASN284, LYS568, TYR648, LYS574, LYS680, THR676, GLY675, GLU672, SER674, ALA573, VAL455, THR378, LEU136, PHE285, GLU88, ASN282, ASN133, HIS341, ASP283, GLY135, TYR573, ARG569, GLY134, ASN678, GLN665 21 Red Derivat 8 21 -9.50 GLY677 THR676 HIS377 GLY677, THR676, HIS377, ARG569, ASN678, LYS568, LYS574, TYR648, LYS680, GLY675, ARG138, ASN484, SER674, GLU672, ALA673, VAL455, LEU136, THR378, ASP339, ALA383, HIS341, PHE285, ASN284, GLY135, GLY134 22 Un Named 32 -9.11 GLY135 ASP283 GLY675 ASN484 HIS377 GLU672 GLY135, ASP283, GLY675, ASN484, HIS377, GLU672, GLY134, LEU136, THR676, LEU139, VAL455, SER674, ALA673, THR671, THR378, VAL379, ASN284, LEU380, TYR573, LYS574, LYS568, TYR648, ARG569 Volume 14, 2020 Microbiol Indones 61 Table 5 The results of docking pigment tests from Monascus sp. with 2 GPA (Glycogen Phosphorylase) receptor -Continued- No Compounds Run Binding Affinity kkal/mol HydrogenBond Amino Acid (Residue Contact) 23 Monascopyridine A 49 -9.81 LEU136 ASP283 GLY135 GLU672 LEU136, ASP283, GLY135, GLU672, PHE286, ALA383, PHE285, SN284, ASN133, GLY137, GLY134, LYS574, THR676, GLY675, SER674, HIS377, ALA673, THR378, THR671, TYR573, VAL379, LEU380, ASP339, HIS341 24 Monascopyridine B 35 -9.21 HIS377 ALA673 LEU136 ASP283 HIS377, ALA673, LEU136, ASP283, LEU139, TYR573, GLY135, GLY137, GLY134, ASN133, ASN284, ASP339, PHE285, PHE286, ALA383, VAL567, HIS341, GLN665, LYS568, GLY677, ASN678, THR676, GLY675, THR378, GLU672, LYS574, SER674 25 Monascopyridine C 23 -8.59 SER674 GLY675 GLU672 GLY135 LEU136 ASP283 ASN284 SER674, GLY675, GLU672, GLY135, LEU136, ASP283, ASN284, THR378, HIS341, ALA383, PHE285, ASP339, LEU384, LEU139, VAL455, ASN484, ALA673, THR676, HIS377, TYR573, LYS574, GLY134 26 Monascopyridine D 59 -9.03 LEU136 ASP283 ASN284 GLU672 LEU136, ASP283, ASN284, GLU672, HIS341, ASP339, ALA383, PHE285, THR378, SER674, GLY675, ASN484, THR676, LEU139, VAL455, LYS574, ALA673, TYR573, GLY135, HIS377, GLY134 27 New Red Pigment 52 -9.59 ASP283 LEU136 HIS377 ASN484 GLY675 THR676 GLY677 ASP283, LEU136, HIS377, ASN484, GLY675, THR676, GLY677, VAL567, TYR648, LYS574, LYS568, GLY135, ASN284, ASN133, GLU88, GLY137, GLY134, VAL455, LEU139, SER674, ALA673, GLU672 28 Monascuskaodione A 76 -9.48 HIS377 ASN484 GLY675 THR676 HIS377, ASN484, GLY675, THR676, GLY677, LYS574, ASN678, LYS568, GLN665, GLU672, ASN284, ASP238, GLU88, ASN282, ASN133, LEU136, VAL455, LEU139, ALA673, SER674, GLY135 29 Monascuskaodione B 86 -9.46 HIS377 ASN484 GLY675 THR676 HIS377, ASN484, GLY675, THR676, VAL455, LEU139, ALA673, SER674, GLU672, GLY135, GLY677, LYS574, GLY134, LYS568, ARG569, TYR648, ASP283, LEU136, ASN284, ASN133, GLU88, GLY137 30 Red Shandong 1 60 -8.36 HIS377 ASN284 GLU672 HIS377, ASN284, GLU672, ALA673, VAL455, TYR573, LYS574, LEU139, ASN484, GLY675, GLY135, SER674, YHR676, LEU136, ASP283, GLY134, GLY137, GLU88, ASN133, HIS341, ASP339 31 Red Shandong 2 37 -8.15 GLY135 ASP283 LYS574 TYR573 GLY135, ASP283, LYS574, TYR573, HIS377, ASN133, ASN284, THR378, HIS341, ASP339, PHE285, ALA383, LEU136, GLY675, GLU672, THR676, GLY677, ASN678, GLN665, LYS568, VAL567, ARG569, GLY134, HIS571 32 FK 17-P2B2 55 -7.74 HIS377, ASN484, GLY675, GLU672, ASN284 LEU136, HIS377, ASN484, GLY675, GLU672, ASN284, ASN133, GLU88, ASP283, TYR573, GLY135, LYS574, SER674, THR676, ALA673, VAL455, LEU139. 33 Monankarin A-B 42 -8.39 GLU162, GLU273 ARG277, ILE275, VAL278, GLN295, ARG277, ASN274, ILE275, ALA246, SER245, ILE159, ARG160, GLU162, GLU273 34 Monankarin C-D 38 -8.17 VAL567, LYS568, GLU672, GLY675, HIS377, ARG569 LYS574, LEU136, GLN665, GLY677, ASN678, THR676, TYR573, SER674, ALA673, VAL455, ASN284, GLY135, ASP283, GLY134, TYR648, VAL567, LYS568, GLU672, GLY675, HIS377, ARG569 62 YULIANA ET AL. Microbiol Indones Table 5 The results of docking pigment tests from Monascus sp. with 2 GPA (Glycogen Phosphorylase) receptor -Continued- No Compounds Run Binding Affinity kkal/mol HydrogenBond Amino Acid (Residue Contact) 35 Monankarin E 70 -9.14 GLU672, LYS568, GLY135, ASP283, ASN284 LYS574, LEU136, HIS377, GLY134, ARG569, TYR648, VAL567, GLY677, GLN665, ASN678, THR676, GLY675, VAL455, SER674, ALA673, GLU672, LYS568, GLY135, ASP283, ASN284 36 Monankarin F 3 -8.71 GLY135, HIS377, ASN484, GLU672, LYS568, VAL567 LYS574, TYR573, ALA673, TYR648, ARG569, GLY134, LEU136, ASP283, ASN284, THR378, SER674, VAL455, LEU139, GLY675, GLN665, THR676, GLY677, ASN678, GLY135, HIS377, ASN484, GLU672, LYS568, VAL567 37 Monaphilones A 100 -8.46 THR676, GLU672, TYR573, HIS377 LYS568, ARG569, TYR648, LYS680, GLY134, GLY677, GLY135, ASN133, LYS574, ASN284, LEU136, ASP283, GLU88, ASN282, HIS341, VAL455, ALA673, SER674, GLY675, TYR90, THR676, GLU672, TYR573, HIS377 38 Monaphilones B 73 -8.35 LYS568, GLY677, THR676, GLU672, ASN284 TYR648, ARG569, VAL567, GLY134, ASN133, TYR90, ARG649, LYS608, SER674, VAL455, ASN484, GLY135, HIS377, LEU136, GLY675, TYR573, LYS574, LYS568, GLY677, THR676, GLU672, ASN284 39 Monaphilones C 69 -8.82 GLU672, GLY675, ASN484, HIS377 TYR573, LEU380, LYS568, ARG569, TYR648, GLY134, LYS574, THR378, THR671, VAL379, ASN284, ALA673, VAL455, SER674, LEU139, THR676, LEU136, GLY135, GLY677, GLU672, GLY675, ASN484, HIS377 40 Monapurones A 81 -9.55 TYR573, ASN284, THR676, GLY675, ASN484, HIS377, GLU672, LYS568, ALA673, LEU380, VAL379, THR671, THR378, VAL455, LEU139, LEU136, SER674, GLY135, GLY677, ASN678, GLN655, VAL567, LYS574, TYR573, ASN284, THR676, GLY675, ASN484, HIS377 41 Monapurones B 27 -8.35 ASN484, HIS377 LYS568, LEU136, ALA383, VAL567, LYS574, GLY675, TYR573, ASN284, ASP339, THR378, PHE285, HIS341, GLU672, GLY677, THR676, GLY135, LEU139, ALA673, VAL455, SER674, ASP283, ASN484, HIS377 42 Monapurones C 94 -8.17 ASN484, LYS574 GLY675, LYS568, LEU136, SER674, LEU139, GLY135, THR676, GLY677, VAL567, GLN665, TYR573, ASN133, GLU672, ASN282, GLU88, HIS341, ASP283, ASN284, GLY137, THR378, HIS377, GLY134, VAL455, ALA673 43 Monarubrin (Y,BF) 15 -8.57 ASP283, ASN284, GLU672, HIS377 HIS341, GLN665, GLY675, LEU136, LYS568, ASN678, GLY677, THR676, GLY134, LYS574, ARG569, GLY135, TYR573, ALA673, THR378, ASP339, PHE285, ASP283, ASN284, GLU672, HIS377 44 Monascusone A 42 -8-08 ASP283, LEU136, SER674, GLU672 VAL455, ALA673, HIS377, THR378, ASN284, PHE285, HIS341, ASN282, ASN133, GLU88, GLY137, GLY134, GLY135. ASN484, GLY675, TYR573, ASP283, LEU136, SER674, GLU672 45 Monascusone B 23 -9.19 ASN484, HIS377 LEU136, LYS568, HIS341, ALA673, VAL455, LEU139, GLY135, SER674, THR676, VAL567, GLY677, GLU672, LYS574, GLY675, TYR573, ASN284, THR378, GLU88, ASN133, ASN484, HIS377 46 Monascuspiloin 74 -8.32 LYS574, THR676, GLY675, GLU672 TYR648, LYS568, ARG569, GLY134, ASN133, TYR90, LEU136, ALA383, ASP339, THR378, HIS377, ASN284, ALA673, SER674, TYR573, GLY135, GLY677, ASN678, LYS574, THR676, GLY675, GLU672 47 Monashexenoone 31 -9.50 GLU162, GLU273, ARG277, ILE275, TYR161, VAL278, GLN295, ARG277, ASN274, ILE275, ALA246, SER245, ILE159, ARG160, GLU162, GLU273 Volume 14, 2020 Microbiol Indones 63 64 YULIANA ET AL. Microbiol Indones Table 5 The results of docking pigment tests from Monascus sp. with 2 GPA (Glycogen Phosphorylase) receptor -Continued- No Compounds Run Binding Affinity kkal/mol HydrogenBond Amino Acid (Residue Contact) 48 Purpureus one 10 -8.20 LEU136, ASP283, ASN484, GLY675, SER674, GLY677 ARG569, LYS574, GLY135, ASN284, GLY134, TYR90, ASN133, TYR573, HIS377, VAL455, THT676, THR378, LYS680, GLU672, VAL567, TYR648, LYS568, ALA673, LEU136, ASP283, ASN484, GLY675, SER674, GLY677 49 Robropuctin 4 -9.22 GLY672, ASN284, HIS377, GLY135, ASP283 TYR648, ARG569, LYS568, HIS341, TYR90, ASN133, TYR573, ALA673, THR378, ASP339, PHE285, LEU136, LYS574, ALA383, GLY675, GLY134, GLY672, ASN284, HIS377, GLY135, ASP283 50 Xantomonascin A 89 -9.12 HIS377, SER674, LYS574, LEU136, ASP283 HIS341, TYR573, ALA673, THR671, THR378, VAL455, ASN284, ASP339, PHE285, ASN282, GLU88, ASN133, GLY134, ARG569, GLY135, LYS568, THR676, GLU672, GLY675, HIS377, SER674, LYS574, LEU136, ASP283 51 Xantomonascin B 9 -10.13 ASP283, LEU136, THR676, HIS377, SER674 LYS574, ALA383, TYR573, HIS341, ASP339, ASN284, THR378, THR671, ALA673, GLU672, VAL455, GLY675, GLY677, GLY135, ARG569, LYS568, GLY134, ASN133, GLU88, ASN282, PHE285, ASP283, LEU136, THR676, HIS377, SER674 52 Y3 87 -9.29 ASP283, GLY677, THR676 LYS574, LYS568, GLN665, ASN678, GLY675, ALA673, SER674, VAL455, ASN484, LEU139, HIS377, THR378, LEU136, GLY135, ASN133, GLY137, ASN284, GLY134, ARG569, TYR573, GLU672, ASP283, GLY677, THR676 53 Yellow II 64 -8.80 HIS377, LEU136, ASP283 ALA383, HIS341, ASP339, THR378, ALA673, SER674, GLU672, GLY675, THR676, LYS568, GLY677, LYS574, GLY135, GLY134, GLY137, ASN133, ASN282, ASN284, GLU88, PHE285, PHE286, HIS377, LEU136, ASP283 54 Monaphilol A 63 -9.13 ASP283, GLU672, ASN284, HIS377 TYR648, ARG569, LYS568, LEU136, HIS341, PHE285, ASP339, THR378, GLY675, GLY135, TYR573, LYS574, GLY134, ASN133, HIS571, ASN282, ASP283, GLU672, ASN284, HIS377 55 Monaphilol B 15 -8.93 ASP283, ASN284, GLU672 TYR648, ARG569, LYS568, LEU136, HIS341, ASN282, PHE285, ASP339, HIS377, THR378, TYR573, GLY675, GLY135, LYS574, GLY134, ASP283, ASN284, GLU672 56 Monaphilol C 42 -9.96 ASP283, LEU136, THR676, GLU672, GLY675, ASN484, HIS377, LYS574, LYS568, ALA383, HIS341, ALA673, VAL455, SER674, TYR573, THR378, ASN284, PHE285, ASP339, ASN133,GLU88, GLY134, GLY137, VAL576, GLN665, GLY677, ALA673, ASP283, LEU136, THR676, GLU672, GLY675, ASN484, HIS377 57 Monaphilol D 48 -9.94 HIS377, ASN484, THR676, LEU136, ASP283 HIS341, LYS568, GLU672, VAL455, SER674, LEU139, ALA673, TYR573, ASN284, THR378, PHE285, ALA383, ASP339, GLY134, GLY137, GLY135, LYS574, ASN678, GLN665, VAL567, GLY677, GLY675, HIS377, ASN484, THR676, LEU136, ASP283 58 Monasfluor A 87 -8.92 HIS377, ASN484, GLY675, THR676, LEU136, VAL455, LEU139, SER674, ALA673, GLY677, LYS568, ASN678, GLN665, LYS574, GLU672, GLY135, TYR573, ASN284, ASP283, ASN282, GLU88, ASN133, HIS377, ASN484, GLY675, THR676 59 Monasfluor B 16 -9.47 HIS377, ASN484, THR676, HIS377, ASN484, THR676, LEU136, ASN133, GLY134, GLY137, GLU88, ASP283, ASN284, SER667, GLN665, ASN696, LYS568,GLY677, GLY675, LYS574, ASN678, GLY135, ALA673, LEU139, SER674, VAL455. an antidiabetic drug that works on the glycogen phosphorylase receptor. As conclusion, from drug scan test results on the Isolate MPs4 compound have the values t​​ hat fulfill all parameters' requirements such as molecular weight, proton donors, proton acceptors, log p and molar refractory. ADME test results on Isolate MPs4 compounds have the values t​​ hat fulfill all parameters' requirements of Caco2, HIA (Human Intestinal Absorption), as well as on PPB (Plasma Protein Binding). The docking test results on the Isolate MPs4 compound were the best and qualified because it have smaller binding affinity than original ligands and comparative ligands (Glibenclamide). Therefore, MPs4 isolate can be used as a candidate for new antidiabetic drugs, but still requires further research, including In vitro and In vivo tests. REFERENCES Fatimah RN. 2015. Diabetes melitustipe 2 [Type 2diabetes mellitus]. Artikel Review Medical Faculty Lampung University. 4(5):94. Lelita R, Gunawan R, Astuti W. 2017. 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