Catatan Drug Discovery

catatan_dd.txt

libraries:
-torchdrug
-deepchem

*) pytorch lebih stabil dan reliable daripada tensorflow, biasanya

*) ada 2 approach terhadap NN-based drug design: SMILES-based dan graph-based dimana molekulnya dimodelkan sebagai graph.

BioAssays of GLP-1: https://pubchem.ncbi.nlm.nih.gov/gene/2740#section=BioAssays

https://www.linkedin.com/advice/1/what-techniques-can-you-use-evaluate-deep-rgype

GRAPH-AF mungkin ada memory leak / kurang cache empty karena sering memenuhin VRAM

papers:

- Graph Convolutional Policy Network for
Goal-Directed Molecular Graph Generation

- GRAPH AF

videos:

- biologi, sistem endokrin

- drug discovery development process

- ligand-based & stucture-based virtual screening (kita prioritaskan structure-based karena reseptor GLP-1 sudah ada strukturnya, lihat file pdb atau pdbqt nya seperti https://www.rcsb.org/structure/5olu)

- autodock tools + autodock vina tutorials 

- grpah neural networks

- https://www.youtube.com/watch?v=fMbVB_huh28

- https://www.youtube.com/watch?v=fzSL7MWfXtQ

- https://www.youtube.com/watch?v=qH3z5GwccxE


___




useful databanks:

    NCBI (National Center for Biotechnology Information):
        Website: https://www.ncbi.nlm.nih.gov
        Contains databases like GenBank, PubMed, and BLAST for genetic sequences and biomedical literature.

    UniProt (Universal Protein Resource):
        Website: https://www.uniprot.org
        Comprehensive resource for protein sequence and annotation data.

    KEGG (Kyoto Encyclopedia of Genes and Genomes):
        Website: https://www.genome.jp/kegg
        Database for understanding high-level functions and utilities of biological systems.

    Pfam (Protein Families Database):
        Website: https://pfam.xfam.org
        Collection of protein families and domains.

    DrugBank:
        Website: https://www.drugbank.ca
        Comprehensive database containing information on drugs and drug targets.

    ChEMBL:
        Website: https://www.ebi.ac.uk/chembl
        Database of bioactive molecules with drug-like properties.

    PDB (Protein Data Bank):
        Website: https://www.wwpdb.org
        Repository for 3D structural data of proteins and nucleic acids.

    Ensembl:
        Website: https://www.ensembl.org
        Provides genome data for vertebrates and other eukaryotic species.

    InterPro:
        Website: https://www.ebi.ac.uk/interpro
        Integrates protein signature data from various databases into a single searchable resource.

    BioGRID (Biological General Repository for Interaction Datasets):
        Website: https://thebiogrid.org
        Database of protein and genetic interactions.

    STRING (Search Tool for the Retrieval of Interacting Genes/Proteins):
        Website: https://string-db.org
        Database of known and predicted protein-protein interactions.

    GEO (Gene Expression Omnibus):
        Website: https://www.ncbi.nlm.nih.gov/geo
        Repository for gene expression data.

    ZINC Database:
        Website: http://zinc.docking.org
        Free database of commercially available compounds for virtual screening.

    ExPASy (Expert Protein Analysis System):
        Website: https://www.expasy.org
        Bioinformatics resource portal that provides access to scientific databases and software tools.


# glossary (tidak terurut tapi saran saya, baca dari bawah ke atas)

sistem endokrin: mengeluarkan hormon pada saluran darah

endocrine system: messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. 

diabetes: penyakit pada sistem endokrin disebabkan oleh pankreas yang tidak memproduksi cukup insulin, atau sel-sel tubuh menjadi tidak responsif terhadap efek hormon.

binding thermodynamics: bagaimana suatu obat menginteraksi dengan target

alkene (or olefin): hydrocarbon containing a carbon–carbon double bond (C=C)

steroid: organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and as signaling molecules

endogenous: endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell

intercalation: reversible inclusion or insertion of a molecule (or ion) into layered materials with layered structures. Examples are found in graphite and transition metal dichalcogenides.

structural analog (chemical analog, analog): compound having a structure similar to that of another compound, but differing from it in respect to a certain component.

nucleic acid analogue: compounds which are analogous (structurally similar) to naturally occurring RNA and DNA, used in medicine and in molecular biology research 

ADME: acronym for absorption, distribution, metabolism, and excretion

sugar: generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. 

monomer: molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.

biomolecule: loosely defined as a molecule produced by a living organism and essential to one or more typically biological processes

carbohydrate: biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water)

monosaccharide: the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. Simply, this is the structural unit of carbohydrates.

disaccharides: Compound sugars, also called disaccharides or double sugars, are molecules made of two bonded monosaccharides

pentose: monosaccharide with five carbon atoms.

phosphate: phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid, a.k.a. phosphoric acid H3PO4. 

nucleotide: organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

Nucleotide base (nitrogenous base, nucleobases): nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)

deoxy sugar: sugars that have had a hydroxyl group replaced with a hydrogen atom.

ribose: simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, d-ribose, is a component of the ribonucleotides from which RNA is built, and so this compound is necessary for coding, decoding, regulation and expression of genes. 

moiety: part of a molecule that is given a name because it is identified as a part of other molecules as well. Typically, the term is used to describe the larger and characteristic parts of organic molecules, and it should not be used to describe or name smaller functional groups of atoms that chemically react in similar ways in most molecules that contain them.

substituent: one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms substituent and functional group, as well as side chain and pendant group, are used almost interchangeably to describe those branches from the parent structure, though certain distinctions are made in polymer chemistry.

functional group: substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest of the molecule's composition.

hydroxy group (hydroxyl): functional group with the chemical formula −OH and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy groups.

deoxyribose: monosaccharide with idealized formula H−(C=O)−(CH2)−(CHOH)3−H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of a hydroxy group

nucleic acids: large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is deoxyribose, a variant of ribose, the polymer is DNA. 

base pairs: fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds

exogenous: exogenous substances and processes are those that originate from outside of an organism. 

progesterone receptors (NR3C3): protein found inside cells. It is activated by the steroid hormone progesterone. 

progestogen (also progestins, progestagens or gestagens): class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR)

hormone: class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior

steroid hormones: steroid that acts as a hormone

sex hormone: steroid hormones that interact with vertebrate steroid hormone receptors

embryogenesis: genesis of embrios

progesterone: endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species

parent structure: the structure of an unadorned ion or molecule from which derivatives can be visualized

pregnane: C21 steroid and, indirectly, a parent of progesterone

pregnene: an alkene derivative of a pregnane

cortisone: pregnene (21-carbon) steroid hormone

agonist: molecule that binds to a receptor and activates it, mimicking the effect of a natural ligand or neurotransmitter such as neurotransmitters (e.g., acetylcholine), hormones (e.g., insulin), or morphine.

antagonist: molecule that binds to a receptor but does not activate it. Instead, it blocks or dampens the action of an agonist or endogenous ligand. Examples include naloxone, which blocks opioid receptors to counteract opioid overdose.

cortisol: steroid hormone that is produced by your 2 adrenal glands, which sit on top of each kidney

isomers: molecules with the same chemical formula but have different structures

tautomer: isomers differing only in the positions of hydrogen atoms and electrons

amino:  compounds and functional groups that contain a basic nitrogen atom with a lone pair. (Amine is R-NH2)

carboxylic acid: organic acid that contains a carboxyl group (−C(=O)−OH) attached to an R-group. The general formula of a carboxylic acid is often written as R−COOH or R−CO2H, sometimes as R−C(O)OH with R referring to an organyl group (e.g., alkyl, alkenyl, aryl), or hydrogen, or other groups.  

amino acids:  organic compounds that contain both amino and carboxylic acid functional groups.

amide: compound with the general formula R−C(=O)−NR′R″, where R, R′, and R″ represent any group, typically organyl groups or hydrogen atoms.

covalent bond: chemical bond that involves the sharing of electrons to form electron pairs between atoms. 

peptide bonds (eupeptide bond): amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein chain.

peptide: short chains of amino acids linked by peptide bonds

polypeptide: longer, continuous, unbranched peptide chain

peptide hormone: hormones whose molecules are peptides. These hormones have an effect on the endocrine system of animals, including humans

amylins (islet amyloid polypeptide (IAPP)): A 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin)

Langerhans cell: tissue-resident macrophage of the skin once thought to be a resident dendritic cell

beta cells (β-cells, beta-cells): specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin

pancreatic islets (islets of Langerhans): regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans 

gene: In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes.

lipid: broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing energy, signaling, and acting as structural components of cell membranes.

metabolism: set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks of proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. 

catabolism (catabolic): the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, nucleic acids, and proteins) into smaller units (such as monosaccharides, fatty acids, nucleotides, and amino acids, respectively). Catabolism is the breaking-down aspect of metabolism, whereas anabolism is the building-up aspect. 

anabolism (anabolic):set of metabolic pathways that construct macromolecules like DNA or RNA from smaller units.  These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-down aspect. Anabolism is usually synonymous with biosynthesis.

insulin: peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body.

diabetes type 2 target proteins: https://iopscience.iop.org/article/10.1088/2043-6262/3/1/013001/pdf

ATP (Adenosine Triphosphate): primary energy carrier in all living organisms. It stores and supplies the cell with needed energy. It is composed of adenine, ribose (a sugar), and three phosphate groups. ATP releases energy when it is hydrolyzed to ADP (adenosine diphosphate) and inorganic phosphate. This energy is used for various cellular processes, including muscle contraction, protein synthesis, and cell division.

ADP (Adenosine Diphosphate): product of ATP dephosphorylation, which releases energy. It is composed of adenine, ribose, and two phosphate groups. ADP can be converted back into ATP by the addition of a phosphate group, a process that occurs during cellular respiration and photosynthesis. This conversion is crucial for maintaining the energy balance within the cell.

NAD (Nicotinamide Adenine Dinucleotide): coenzyme found in all living cells. It plays a key role in redox reactions, carrying electrons from one reaction to another. It is composed of two nucleotides joined through their phosphate groups, with one nucleotide containing an adenine base and the other containing nicotinamide. In its oxidized form (NAD+), it acts as an electron acceptor in metabolic reactions, becoming NADH. This conversion is vital for the production of ATP in cellular respiration.

NADH (Reduced Nicotinamide Adenine Dinucleotide): reduced form of NAD+. It carries electrons to the electron transport chain in mitochondria, where it contributes to the generation of ATP. Its structure is similar to NAD+ but in a reduced state, meaning it has gained electrons. NADH donates electrons to the electron transport chain, which drives the production of ATP. This process is a critical part of aerobic respiration.

NADP+ (nicotinamide adenine dinucleotide phosphate, or TPN, triphosphopyridine nucleotide):  cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form, whereas NADP+ is the oxidized form. NADP+ is used by all forms of cellular life

NADPH (Nicotinamide Adenine Dinucleotide Phosphate): coenzyme used in anabolic reactions, such as lipid and nucleic acid synthesis, which require reducing power. Its structure is similar to NADH but has an additional phosphate group. NADPH provides the reducing power needed in biosynthetic reactions and in the defense against oxidative stress. It is primarily generated in the pentose phosphate pathway. 

NADK (NAD Kinase): enzyme that catalyzes the phosphorylation of NAD+ to form NADP+. This phosphorylation is crucial for maintaining the balance of NAD+/NADH and NADP+/NADPH, which are essential for cellular metabolism and the regulation of oxidative stress.

counterions of salt: In table salt (NaCl, also known as sodium chloride) the sodium ion (positively charged) is the counterion for the chloride ion (negatively charged) and vice versa.

solubility: seberapa dapat suatu obat dapat larut dalam air

lipophilicity: seberapa dapat suatu obat dapat larut dalam fat/oil/lipid/non-polar solvents (hexane/toluene)

ADMET properties of drugs: biochemistry acronym for absorption, distribution, metabolism, excretion, and toxicity

software simulasi molecular docking: AutoDock Vina (https://bioinformatics.stackexchange.com/questions/19637/how-to-select-the-best-ligands-in-a-virtual-screening-matrix)

ligand: banyak obat sintetik dibikin untuk nge-bind kepada target spesifik, seperti protein atau enzim, akting sebagai ligand. ligand adalah molekul yang nge-bind ke suatu protein dengan affinitas tinggi dan specificity

protein: molekul besar terdiri dari amino acid

enzim: protein spesial yang mempercepat reaksi kemikal dengan mengurangi energi aktivasi yang diperlukan untuk reaksinya

lipid: kategori compound organik yang tidak dapat larut dalam air termasuk lemak, wax, minyak, hormon, dan beberapa bagian membrane. lipid berfungsi sebagai energy-storage molecule & chemical messengers. lipid terdiri dari oxigen, karbon, & hidrogen

high-throughput screening (hts, high throughput screening): method for scientific discovery especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handling devices, and sensitive detectors, high-throughput screening allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests. Through this process one can quickly recognize active compounds, antibodies, or genes that modulate a particular biomolecular pathway. 

assay: investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The measured entity is often called the analyte, the measurand, or the target of the assay.  An assay usually aims to measure an analyte's intensive property and express it in the relevant measurement unit (e.g. molarity, density, functional activity in enzyme international units, degree of effect in comparison to a standard, etc.). 

bioassay: analytical method to determine the potency or effect of a substance by its effect on living animals or plants (in vivo), or on living cells or tissues (in vitro)

Glucagon-like peptide-1 (GLP-1): A 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region. 

diabetes mellitus: group of common endocrine diseases characterized by sustained high blood sugar levels

Type 2 diabetes (T2D, T2DM, type 2 diabetes mellitus): Form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin.