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Computitional chemistry.pptx

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Computitional chemistry.pptx

  1. 1. A presentation on the topics of Physicochemical, spectral, molecular docking and ADMET studies of Paracetamol; A computational approach Submitted by MD. Ariful Islam ID No: 16209017 Submitted to Md. Moazzam Hossain Lecturer Dept. ACCE Chittagong University Course no: ACCE-509 Date of submission: 1st November, 2022
  2. 2. WHAT IS PARACETAMOL? Generic Name: Paracetamol Commonly called as: PCM Alternate Name: Acetaminophan Paracetamol (PCT) or acetaminophen is one of the most commonly used analgesic and antipyretic drugs with relatively little anti-infammatory activity. Paracetamol is commonly prescribed to relieve pain and fever. Paracetamol treats following condition/s: 1. Fever 2. Pain 3. Osteoarthritis 4. Lower Back Pain 5. Headache 6. Toothache 7. Menstrual Period Pain 8. Cold/ Flu Pain
  3. 3. 1. Fever It is widely prescribed to relieve fever in person of all ages. Paracetamol isprescribed in children if temperature is greater than 38. 5 Celsius or 101.3 Fahrenheit. 2. Pain It is also prescribed to relieve mild to moderate pain. 3. Osteoarthritis Some studies state that paracetamol is also used to treat arthritis pain of knee,hand or hips. 4. Lower Back Pain It is first line treatment of lower back pain Fever Pain
  4. 4. 5. Headache Swiss, Austrian and German headache societies state that Paracetamol with caffeine is also used in Headache. In India paracetamol is also prescribed to relieve headache.Paracetamol is also used to relieve migraine in some countries. 6. Toothache Some studies show that paracetamol is also used in pain of tooth. 7. Menstrual Period Pain Paracetamol is often prescribe with Dicyclomine Hydrochloride or Mefenamic Acid to relieve pain during menstrual period. 8. Cold/ Flu Pain Paracetamol is also prescribed Fig:Headache Fig:Toothache
  5. 5. A computational approach Methods and materials Geometry optimization Protein preparation, docking simulation, analysis and visualization ADMET and Biological activities Geometry optimization Where is it used? Experimental and theoretical investigations in the fields of  chemical structure  thermodynamics chemical kinetics Spectroscopy others Q:Why Geometry optimization is necessary? to know the physical significance of the obtained structure.
  6. 6. Geometry Calculation Gap​(ΔE) = [εLUMO - εHOMO]; Hardness η = [εLUMO - εHOMO]/2; Softness S =1/η; Chemical potential μ =[εLUMO + εHOMO]/2;  Geometry Calculation is done with the help of
  7. 7. Protein preparation, docking simulation, analysis and visualization How is Protein preparation done? By 1. erasing water molecules hetero atoms inactive chain 2. adding hydrogen atoms Why is Molecular docking used? To predict the predominant binding mode(s) of a ligand with a target protein.
  8. 8. ADMET and Biological activites Refers to Chemical absorption Distribution Metabolism Excretion toxicity AdmetSAR online server is used to predict the ADMET properties of all drugs PASS online server is utilized to predict the biological properties
  9. 9. Software required for the Computitional Approach 1.Gaussian 09W 9.5 Revision D.01 2.GaussView 6.0.16 Win64 3.GaussSum-3.0.2-amd64 4.BIOVIA_2021.DS2021 5.Chimera-1.16 6.OriginPro 2016 SR0 b9.3.226 7.PyMoL22 8.SWISS-PDB
  10. 10. Which includes the following Thermodynamic analysis Molecular orbital analysis Molecular electrostatic potential analysis Molecular electrostatic potential analysis Vibration frequency analysis UV-Vis spectral analysis Docking (Binding affinity) and non-bonding interaction analysis ADMET analysis Biological activities prediction Results and discussion
  11. 11. Thermodynamic analysis Free energy and enthalpy are related to the absorption or release of energy chemical stability of a molecule. •The negative sign reveals the spontaneous binding and the high value alludes to the more available bindings. The dipole moment describes electronic property. Higher the dipole moment value higher the intermolecular interactions along with more polar in nature.
  12. 12. Molecular orbital analysis Fig: HOMO LUMO and band gap Fig: DOS plotting HOMO LUMO and Band Gap HOMO–LUMO gap referes chemical hardness softness. Larger HOMO–LUMO gap related to high kinetic stability low chemical reactivity. Small HOMO–LUMO gap is important for low chemical stability
  13. 13. Molecular electrostatic potential analysis Fig: Molecular electrostatic potential
  14. 14. Used to parametrize force fields for classical molecular dynamics simulations Mulliken and NBO methods have been utilized to compute the atomic partial charges. Atomic partial charge FT-IR spectral analysis to investigate any chemical structures which confirm the presence of different functional groups in the molecule Show peak in range of 400-4000 cm-1 Vibration frequency analysis Fig: FT-IR spectra of paracetamol
  15. 15. UV-Vis spectral analysis Two characteristic electronic transition states is seen. Kinetic stability and reactive sites depend on the first electronic transition from the ground state (S0) to singlet (S1). Paracetamol shows broad absorption bands at 266.85 nm along with its oscillator strength 0.0083. Fig: UV-Vis spectral analysis of paracetamol
  16. 16. Greater negative values of binding affinity indicate stronger binding between drugs and the receptor protein. Strong hydrogen bonding is the most significant contributing factor in increasing binding affinity of drugs with the receptor. Hydrogen bond of < 2.3 Å are able to increase the binding affinity. The binding affinity of Paracetmol is − 6.2 kcal mol−1 Docking (Binding affinity) and non-bonding interaction analysis
  17. 17. Fig: Docked conformation of PCT at inhibition bounding site receptor protein 5F19 (Chain A) Fig: Non-binding interaction of paracetamol
  18. 18. Figure: (a) H-bond surface of 5F19 with paracetamol (b) Charge surface of 5F19 with paracetamol (c) Hydrophobicity surface of 5F19 with paracetamol (d)Solvent accessibility(SAS) surface of 5F19 with paracetamol (e) Ionizability surface of 5F19 with paracetamol
  19. 19. ADMET analysis The structure shows positive response for blood brain barrier (BBB) criteria Predicting that drugs can pass through the BBB PCT shows no inhibitory property for human
  20. 20. Biological activities prediction The PASS prediction is used to predict more than 1000 biological and toxicological studies the prediction result is denoted by Pa (probability of compound being active) and Pi (probability of compound being inactive) Value Prediction Pa > 0.7 likely show the experimental activity a known pharmaceutical agent 0.5 < Pa < 0.7 likely show the experimental activity unlike known pharmaceutical agents Pa < 0.5 unlikely to show the experimental activity Increasing the chance of new compound
  21. 21. Properties Probability of compound being active Analgesic stimulant 0.793 Antiinflammatory 0.319 Methemoglobinemia 0.278 It is clear that these compounds have more antipyretic, anti- inflammatory and analgesic activities
  22. 22. Computational tools are becoming popular in drug discovery and development to predict unknown properties of new chemicals. Conclusion It can predicts the following without performing any costly experiment Geometrical thermodynamical molecular orbital Spectral biological features

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