Adobe Systems Computer model of a molecule 1 Radka Svobodová Adobe Systems Content 2 •Introduction: concept of chemoinformatics, content of the subject, history of the field •Computer model of a molecule: 1D, 2D and 3D structure, molecule representation using graph and matrix •2D structure (topology) of a molecule: •writing a molecule using a string (SMILES, InChi, InChiKey) •Molecular graphs: Isomorphism and canonical indexing •3D structure (geometry) of the molecule: •representation using Cartesian and internal coordinates, data formats, geometry comparison http://www.rcsb.org/pdb/images/MAN_600.gif Adobe Systems Basic chemical terms I •Atom: basic building block from which substances are formed • •Structure of an atom: •Atom core: protons (positive charge), neutrons (no charge) •Electron shell: electrons (negative charge) • • Bohr model | Description, Hydrogen, Development, & Facts | Britannica 3 Adobe Systems Basic chemical terms II •All systems tend to occupy the state with the lowest possible total energy. 4 Adobe Systems Basic chemical terms III •The space of the electron shell can be divided into so-called layers. •All electrons in a layer have the same energy value (this energy is characteristic of that layer). •The further the layer is from the nucleus, the higher the energy of the electrons in it. •The electrons in the electron shell therefore fill first the layer closest to the nucleus (the most energetically favorable), then the second closest, and so on. Bohr model | Description, Hydrogen, Development, & Facts | Britannica 5 Adobe Systems Basic chemical terms IV •The non-empty layer that is farthest from the core is called the valence layer. •In this layer are the so-called valence electrons. • •These valence electrons are the subject of the study of chemistry because they can participate in chemical bonding. Bohr model | Description, Hydrogen, Development, & Facts | Britannica 6 Adobe Systems Basic chemical terms V •Chemical bond: •Two atoms come together at a sufficiently small distance (bonding distance) => overlapping of their electron shells. •The valence electrons of both atoms change their trajectories. •If the resulting system has a lower energy than the original, the atoms remain at bonding distance => chemical bonding is formed. 7 Adobe Systems Basic chemical terms VI •Bond order: •single bond: two valence electrons are involved (binding electron pair) •double bond: two bonding electron pairs are involved •Triple bond: analogous •higher multiplicities do not occur in real chemical environments •Aromatic bond: when single and double bonds alternate, the electrons are delocalised among them. These bonds have properties between single and double bonds. Vektorová grafika „Covalent bonds [Single, double, triple]“ ze služby Stock | Adobe Stock 8 Adobe Systems Basic chemical terms VII •Molecule: A system of atoms joined together by bonds to form a single unit. The basic structural unit of a substance. The carrier of the chemical properties of a substance. •Example: adenosine triphosphate (ATP) Molekula Nukleotid Atp - Obrázek zdarma na Pixabay - Pixabay 9 Adobe Systems Basic chemical terms VIII •Molecular system: A system containing one or more molecules. • •Example: Molecular recognition - Wikipedia 10 Adobe Systems Basic chemical terms IX •Organic molecules: •Their main component is carbon, the only element that is able to form longer chains of the (-C-)n type, n > 10. •This property of carbon allows the formation of complex molecules - the building blocks of living systems. •Organic molecules also contain elements: H, O, S, N, F, Cl, Br, I • •Inorganic molecules: •All molecules, that are not organic. Differences Between Organic and Inorganic Molecules - YouTube 11 Adobe Systems 12 How to describe a molecule in a computer? •Find out which information describes the molecule •Write them into the computer about 12 Adobe Systems Which information describes the molecule? Number of atoms? 13 Adobe Systems Which information describes the molecule? Number of atoms? Not enough Number of atoms and positions of bonds? 14 Adobe Systems Which information describes the molecule? Number of atoms? Not enough Number of atoms and positions of bonds? Better Number of atoms, positions of bonds and positions of atoms in 3D space? Yes 15 Adobe Systems Model of molecule for computer processing Atoms: •Points in space •Chemical symbol of the element listed for each Bonds: •Pairs of atoms that are bonded •Bond order 16 Adobe Systems Description of a molecule in a computer 17 Adobe Systems Challenge: Draw this molecule. What is the name of the molecule? 18 Adobe Systems 28.10.2024 Databases of small organic molecules 19 > 1 M structures of small molecules §Small molecule: < 100 atoms §Small molecules = “drug-like” molecules §Experimental structures §Predicted (computed) structures PubChem Drugbank - A New Tech Startup | Edmonton Global ChEMBL is 10 years old in 2019! 19 Adobe Systems DrugBank – database of drugs A screenshot of a cell phone Description automatically generated 20 Adobe Systems 28.10.2024 DrugBank – database of drugs 21 Adobe Systems PubChem – database of organic molecules A screenshot of a cell phone Description automatically generated 22 Adobe Systems 28.10.2024 PubChem – database of organic molecules 23 23 Adobe Systems Ligand Expo – database of ligands Ligand = molecule bound in a protein 24 24 Adobe Systems Ligand Expo – database of ligands Ligand = molecule bound in a protein 25 25 Adobe Systems Databases of biomacromolecules 26 Mainly proteins > 200 k experimental structures > 200 M computed structures 26 Adobe Systems Protein Data Bank – sources of data 27 10% NMR spectroscopy 1% cryoelectron microscopy 89% X-ray crystallography ... ATOM 46 C GLY A 70 51.536 23.360 40.507 ATOM 47 O GLY A 70 50.947 22.279 40.325 ATOM 48 N ILE A 71 50.965 24.532 40.270 ATOM 49 CA ILE A 71 49.595 24.644 39.786 ... 3D struktura https://cdn.rcsb.org/pdb101/motm/images/tn/197-Zika_Virus-5ire_glyc-tn.png https://cdn.rcsb.org/pdb101/motm/images/2wdk_2wdl_front.jpg Výsledek obrázku pro CYTOCHROME C450 27 Adobe Systems Protein Data Bank 28 > 225 000 biomacromolecular structures 28 Adobe Systems Protein Data Bank A screenshot of a computer Description automatically generated 29 Adobe Systems Protein Data Bank A screenshot of a computer Description automatically generated 30 Adobe Systems Protein Data Bank 31 a-helix b-sheet Scabin 6vv4 Adobe Systems Prediction of protein structures by AlphaFold 32 Structures generated by artificial intelligence § https://predictioncenter.org/casp14/doc/presentations/2020_11_30_CASP14_Introduction_Moult.pdf Structure prediction challenge 2020: AlphaFold2 wins 32 Adobe Systems Prediction of protein structures by AlphaFold 33 Structures generated by artificial intelligence § > 200M protein structures 33 Adobe Systems Exercises •Search the PubChem database for a testosterone molecule: •See its 2D structure. How many O's does it have? •Look at its 3D structure. Is any of its cycles planar? •Look at its SDF file. What are the x, y, and z coordinates of the first atom? •Search the DrugBank database for a penicillin molecule: •How many S atoms does it have? •Are any of its cycles planar? •Look at its SDF file. What 2 atoms form the first bond? •Search the LigandExpo database for a fructose molecule: •How many double bonds does it has? •How many C's are off cycle? •Look at its SDF file. What are the coordinates of the first hydrogen? •Look up the green mamba venom molecule in the Protein Data Bank: •How many beta-sheets does it have? •Look at the PDB file. Which amino acid is the first? 34 Adobe Systems 35 Thank you for your attention Bioinformatics Chemoinformatics Tools Databases AI http://www.rcsb.org/pdb/images/MAN_600.gif