Computer aided drug designe objective
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The document outlines various concepts and software related to computer-aided drug design, including quantum mechanics and molecular mechanics operations, energy minimization, conformational analysis, and the design of drug molecules. It contains multiple-choice questions on topics like molecular dynamics, bioisosterism, QSAR, and docking methods in drug discovery. The content serves as an educational resource for students and professionals in medicinal chemistry and computational drug design.
Computer aided drug designe objective
- 1. COMPUTER AIDED DRUG DESIGNE BP807ET PREPARED BY: MANOJ KUMAR YADAV ASSISTANT PROFESSOR (MEDICINAL CHEMISTRY) PIT, JAUNPUR manojniperrbl@gmail.com 01) Which of the following operations or calculations would generally be carried out using quantum mechanics? a. Energy minimisation b. Identifying stable conformations c. Partial atomic charges d. Energy calculations for specific conformations 02) Which of the following software programs is not used for drawing 2D chemical structures? a. ChemDraw b. ChemWindow c. Chem3D d. Isis/Draw 03) Which of the following software programs is not dedicated to the creation of 3D chemical models? a. DOCK b. Alchemy c. Hyperchem d. Discovery Studio Pro 4. Which of the following is associated with conformational searching? a. LUDI b. DOCK c. Monte Carlo method d. CoMFA 5. Molecular dynamics can be used to search for different conformations of a molecule. Which of the following statements is false? a. A variety of different conformations are generated by 'heating' the molecule to 900K. b. The position and velocity of each atom is measured after each nanosecond of movement
- 2. COMPUTER AIDED DRUG DESIGNE BP807ET c. The programme treats each atom as a moving sphere d. Each atom is only allowed to move a fraction of a bond length between each cycle of calculations 6. Which of the following statements regarding molecular mechanics is untrue? a. It treats atoms as spheres. b. It treats bonds as rigid features. c. It is a molecular modelling computational method. d. It uses equations that obey the laws of classical physics. 7. Which of the following statements regarding quantum mechanics is untrue? a. It uses quantum physics to calculate molecular properties. b. It makes the assumption that nuclei are moving independently of each other c. It makes the assumption that electrons move independently of each other. d. There are two broad categories - ab initio and semi-empirical 8. Which of the following statements is true? a. energy minimisation is carried out using molecular mechanics b. energy minimisation is used to find the most stable conformation for a molecule c. energy minimisation is carried out by varying only bond angles and bond lengths d. energy minimisation stops when a structure is formed with a much greater stability than the previous one in the process 9. What is meant by a local energy minimum in conformational analysis? a. it is a localised region of a molecule which is free of steric strain b. it is the most stable conformation of a structure c. it is the initial structure that is formed when a 3D model is created, prior to energy minimisation d. it is the closest stable conformation to the starting structure 10. What is meant by a global energy minimum in conformational analysis? a. It is a localised region of a molecule which is free of steric strain. b. It is the most stable conformation of a structure. c. It is the initial structure that is formed when a 3D model is created, prior to energy minimisation. d. It is the closest stable conformation to the starting structure. .
- 3. COMPUTER AIDED DRUG DESIGNE BP807ET 11. The following diagram shows the energy of the starting structure prior to energy minimisation. What is the likely result of energy minimisation? a. Energy minimisation would have no effect and the structure would remain at position Y. b. The structure would be energy minimised and give the most stable structure corresponding to position Z. c. The structure would be energy minimised and give a final structure corresponding to either position X or Z. d. Energy minimisation would be carried out and the final structure would correspond to position J. 12. Which of the following statements regarding structural overlays is false? a. The two structures to be overlaid should both be in their active conformations. b. Usually specific pairs of atoms are chosen (one from each molecule) to allow the overlay to take place. c. The fitting process normally involves both molecules being rigid and not changing conformation during the overlay. d. The overlay is carried out until a maximum value of the root mean square distance between all the atom pairs is achieved. 13. Which of the following statements is true? a. The most stable conformation of a drug is not necessarily the active conformation. b. The active conformation is the most reactive conformation of a structure. c. The active conformation is the conformation adopted by a target binding site when it binds a drug. d. The active conformation can be determined by conformational analysis.
- 4. COMPUTER AIDED DRUG DESIGNE BP807ET 14. Which of the following statements is not true of cyclic structures? a. They are normally more rigid than acyclic structures b. They have fewer possible conformations c. They are useful in determining the active conformation of a series of related compounds d. . They are easierto synthesise than more flexible acyclic molecules 15. What term is used to describe the process by which drugs are fitted into their target binding sites using molecular modelling a. Energy minimisation b. Conformational searching c. Docking d. Overlaying 16. What term is used for the design of a novel drug based on molecular modelling studies of a binding site a. Drug development b. Structure-based drug design c. De novo drug design d. Drug optimisation 17. Which of the following statements is false in de novo drug design? a. The design of flexible molecules is superior to rigid ones. b. Molecules should be designed to fit as snugly as possible into the target binding site. c. Molecules that have to adopt an unstable conformation in order to bind should be rejected. d. Desolvation energies cannot be ignored. 18. What is the software LUDI used for? a. Docking molecules into binding sites b. Automated de novo drug design c. Creating 3D models of molecules d. Conformational analysis 19. Which of the following statements is untrue when using molecular modelling to design a combinatorial library?
- 5. COMPUTER AIDED DRUG DESIGNE BP807ET a. Pharmacophore triangles can be used to design a library. b. The aim is to synthesise the maximum number of structures likely to produce the minimum number of pharmacophores. c. Rigid structures should be analysed before flexible ones. d. Structures should only be included in the library if they represent at least 10% additional new pharmacophores compared to the total represented by structures already present in the library. 20. Which of the following operations or calculations would generally be carried out using molecular mechanics? a. Heat of formation for specific conformations b. Generating different conformations c. Partial atomic charges d. Transition-state energies 21. Which of the following operations or calculations would generally be carried out using quantum mechanics? a. Studying molecular motion. b. Generating different conformations. c. Energy minimisation. d. Transition-state energies. 22. Which of the following software programmes is not used for drawing 2D chemical structures? a. ChemDraw b. LUDI c. ChemWindow d. Isis/Draw 23. Which of the following software programmes is not dedicated to the creation of 3D chemical models? a. CAChe b. CoMFA c. ChemX d. Sybil
- 6. COMPUTER AIDED DRUG DESIGNE BP807ET 24. Which of the following statements is false regarding Monte Carlo methods of conformational searching? a. The Monte Carlo method introduces a bias towards stable conformations. b. The method has the drawback that the structure becomes stuck in a local energy minimum 'well' and fails to reach the global energy minimum. c. Energies of randomly created conformations are compared, then further minor modifications are carried out on the more stable conformations. d. Random conformations are generated by carrying out bond rotations 25. Molecular dynamics can be used to search for different conformations of a molecule. Which of the following statements is false? a. A variety of different conformations are generated by 'heating' the molecule to 900K. b. The position and velocity of each atom is measured after each femtosecond of movement. c. The programme treats each atom as a moving sphere. d. Each atom is only allowed to move a bond length between each cycle of calculations. 26. Two molecules or molecular fragments containing an identical number and arrangement of electrons should have similar properties are: a. Isosteres b. Isomers c. Isotopes d. None of above 27. Tolbutamide, an oral hypoglycemics agent having extended half-lives and with reduced toxicity has been designed by replacement of: a. Chlorine b. Methyl c. Amino d. Ethyl 28. In 5-fluorouracil, an antineoplastic agent, Fluorine exerts inductive effect and responsible for inhibition of which enzyme: a. Esterase b. Thymidylate synthase c. Folatereductase d. Phosphorylase
- 7. COMPUTER AIDED DRUG DESIGNE BP807ET 29. In cholinergic agonists replacement of quaternary ammonium group with the phosphonium and arsonium analogues include which substitution: a. Univalent substitution b. Divalent substitution c. Trivalent substitution d. Tetravalent substitution 30. The substitution in which steric arrangement and electronic configuration are similar to those of the parent compound a. Isosterism b. Bio-isosterism c. Classical Isosterism d. Non-classical isosterism 31. Pethidine and meperidine areester of a piperidyl carboxylic acid: a. Methyl b. Ethyl c. Propyl d. Butyl 32. By opening of the thiazole ring of the sulphathiazole to give a thioureaqunit, sulphur ato is replaced by which atom a. Oxygen b. Nitrogen c. Carbon d. None of these 33. Which bond of diethyl stilbestrol was important for the orientation of the phenolic and ethyl groups for binding to the estrogenic receptor: a. Upper b. Lower c. Central d. Front
- 8. COMPUTER AIDED DRUG DESIGNE BP807ET 34. In amide group bioisosteres, amide bond is required as: a. Hydrogen donor b. Hydrogen acceptor c. Both (a) and (b) d. None of above 35. Which bioisosteres have been successfully employed in the development of H2- receptor antagonist: a. Amide bioisosteres b. Thioureabioisosteres c. Halogen bioisosteres d. Classical bioisosteres 36. Who is the father of cocept of QSAR a. Corwin Hansch b. Meyer-Overton c. Ferguson d. Richest 37. QSAR helps in drug design as it helps in... ..... .. a) Prediction of biological activity of drug b) Minimizing of side effect c) Optimization of lead d) All of the above 38. EIectric and steric property mainelly helps in a) Absorbtion of drug b) Penetration of drug c) Drug-receptor interaction d) None of the above 39. Organic solvent used in measuring partition-coefficient is... . . . . . . . . . . . . a) Aceton b) n-octanol c) Benzene d) Propranol 40. Ionization of benzoic acid is used in ..... a) Hydrophobic parameter
- 9. COMPUTER AIDED DRUG DESIGNE BP807ET b) Steric parameter c) Electronic parameter d) None of the above 41. DYLOMMS (Dynamic Lattice-Oriented Molecular modelling system) is related to: a) SAR b) 2D-QSAR c) 3D-QSAR d) None 42. Colchicineis a lead compound for agents which act as inhibitor of: a) tubulin polymerization b) Cell wall synthesis c) Protein synthesis d) Metabolites 43. The biological activity of most drugs is related to a combination of physicochemical properties. This statement is relevant to: a) Hammett’s substituent constant b) Tafts steric constant c) Hansch analysis d) Free Wilson analysis 44. Partial Least Square (PLS) is used in: a. SAR b. 2D-QSAR c. 3D-QSAR d. None 45. Xn, an indicator variable is related to: a. Hammett’s substituent constant b. Tafts steric constant c. Hansch analysis
- 10. COMPUTER AIDED DRUG DESIGNE BP807ET d. Free Wilson analysis 46. The measure value of the electron withdrawing or electron donating ability of a substituent is known as: a. Hammett’s substituent constant b. b. Tafts steric constant c. Hansch analysis d. d. Free Wilson analysis 47. The numerical range for the thermodynamic activity which showing that they are active only at relative high concentration is: a. 0.1-1.0 b. 0.01-1.0 c. 0.001-0.01 d. 1-10 48. The positive value of Tt indicates that substituents is: a. More hydrophobic than halogen b. less hydrophobic than halogen c. More hydrophobic than hydrogen. d. less hydrophobic than hydrogen 49. The negative value of It indicates that substituents is: a. More hydrophobic than halogen b. More hydrophobic than hydrogen. c. Less hydrophobic than halogen d. Less hydrophobic than hydrogen 50. An equilibrium is set up between the ionized and unionized forms where the relative properties of these species are known as: a. Equilibrium b. Dissociation constant
- 11. COMPUTER AIDED DRUG DESIGNE BP807ET c. All of above d. None 51. QSAR is.... (a) Quantitative structure activity relationship (b) Quantity structure action result (c) Quality structure action report (d) All of the above 52. Software used in verloop steric parameter is (a) Chemdraw (b) Marwin sketch (c) Argus (d) Sterimol 53. Which parameter is used to find steric property (a) Freewilson (b) Hansch analysis (c) Tafts steric constant (d) Hammett constant 54. In which synthesis Solid support used in combinatorial chemistry a. Liqiud phase synthesis b. Solid phase synthesis c. Phase —I synthesis d. Conventional synthesis 55. An innovative process oi finding new medication based on the knowledge of a biological Target is (a) Drug design (b) New design (c) Modelling (d) New target 56. Hammett’s constant used to find which parameters a. HydrHydrophili
- 12. COMPUTER AIDED DRUG DESIGNE BP807ET b. Electronic c. steric d. Lipopliilie 57. Combinatorial synthesis is Used mainly for the synthesis of a. Beta lacta b. Monobactams c. Tetracycline d. Peptide Polymers 58. Relative distribution of drug in organic and aqueous mixture is Known a. Hydrophilicity b. Hydrophobicity c. Partition coefficient d. Lipophlicity 59. When both ligand and receptor are flexible. The ligand attach flexibly at the active site of receptor to maximize attaching forces between them. This type of docking is known as: a) Induced fit docking b) Lock and key docking c) Ensemble docking d) Rigid docking 60. Multiple protein structures are utilized as an ensemble for docking with ligand in one of the following technique: a) Induced fit docking b) Lock and key docking c) Ensemble docking d) Rigid docking 61. The docking combined with a scoring function can be used to quickly screen large databases of potential drugs in silico to identify molecules that are likely to bind to protein target of interest.This method is helpful for. a) Hit identification b) Lead optimization
- 13. COMPUTER AIDED DRUG DESIGNE BP807ET c) Bioremediation d) Drug-DNA interaction 62. The rotamer libraries of amino acid side chains are used for. a) Ligand flexibility b) Receptor flexibility c) Scoring function d) Search space 63. Force field energy estimation is most often used for: a) Ligand flexibility b) Receptor flexibility c) Scoring function d) Search space 64. Protein-ligand docking goftware congi8tN of two main components which works together are: a) Search Algorithm and Scoring function b) Fragment based algorithm and Scoring function c) Search algorithm and Genetic algorithm d) Fragment based algorithm and Genetic algorithm 65. In molecular biology, there are two docking probletng arise are: a) Protein- protein clocking and Rigid- body docking b) Ligand- protein docking and Protein-Protein docking c) Rigid-body docking and ligand-protein docking d) None of these. 66. Rigid docking include: a) Molecular shape representation b) Surface patch matching c) Filtering and scoring d) All of above 67. E<1 implies for: a) Positive enrichment b) Negative enrichment
- 14. COMPUTER AIDED DRUG DESIGNE BP807ET c) Positive and Negative enrichment d) Constant enrichment 68. Challenges stand up during De novo design. a) Structure generation b) Scoring c) Optimization d) All of above 69. The non-bonded interaction which calculate the low energy conformation of a molecule also known as: a) London interaction b) Van der Waals interaction c) Coulomb interaction d) ‘London-Van der Waal interaction 70. The electron wave function for all the electrons in a molecule tells us: a. Electron rotation b. Electron density c. Electron affinity d. All of above 71. The program which helps to join the templates, such ag five and six membered ring and acyclic fragments to mimic pharmacophore model is: a) SCROUT b) UNITY c) MACCS-3D d) CAVEAT 72. Which program is using as shape based super position for identifying compound that have similar shape: a) CSD b) DBS-3D c) DOCK d) ROCS
- 15. COMPUTER AIDED DRUG DESIGNE BP807ET 73. The model generated from MD deception trajectories show considerably better representation of the flexibility of pharmacophore is: a) Dynamic pharmacophore b) Ligand pharmacophore c) Structural pharmacophore d) Pharmacophore filter 74. Interaction between a charged ion and a neutral molecule with a dipole moment is called: a) Ion-dipole interaction b) Dipole- dipole interaction c) Bonded interaction d) Non-bonded interaction 75. Virtual screening techniques are categorized on the basis of: a) Structure based b) Ligand based c) Fragment based d) Structure and ligand based 76. Quick searching of database of 3D structures programs includes: a) Chem DBS-3D, b) ALLADIN UNITY, c) MACCS-3D d) All of above 77. Name of the program in which fragments from bioactive conformation are joint with spacer to generate a new structure to fit the model. a) SCROUT b) UNTY c) NEWLEAD d) QSAR 78. Virtual Screening is also called as: a. Silico drug design b. Rational drug design c. Serendipity drug design d. None of the above
- 16. COMPUTER AIDED DRUG DESIGNE BP807ET 79. The techniques that hold a lot of prospective in target identification (generally proteins/enzymes), target validation, understanding the protein is called as a) Cheminformatics b) Docking c) Bioinformatics d) None of the above 80. 3-D geometry of interaction features that a molecule must have in order to bind in a protein’s active site is called as a) Inactive compound b) Pharmacophore c) Active compound d) Bioprecursor 81. Following is a type of docking. a) Rigid b) Flexible c) Mannual /Semiflexible d) All of the above 82. Based on the principle of conformation generation, the search methods are categorized into....... a) Stochastic b) Systematic c) Deterministic d) All of the above 83. The field of science in which biology, computer science and information technology merges to form a single discipline is called a) Chemoinformatics b) Bioinformatics c) Rational drug design d) None of the above 84. Representation of 2d molecular structures includes a) Image file b) Graph theory
- 17. COMPUTER AIDED DRUG DESIGNE BP807ET c) Connection table d) All of the above 85. The computerized method to understand and arrange the information associated with biological macromolecules is: a) Chemo-informatics b) Bio-informatics c) Chemical database d) Biochemical database 86. Analysis under the bioinformatics to be done for a component having large dimensionality and small sample size are: a) Sequence analysis b) Spectral analysis c) Microarray analysis d) Small sample domain analysis 87. NIH’s Molecular Libraries and Imaging initiative are the experimental project of: a) Chemoinformatics b) Bioinformatics c) Chemical database d) Biochemical database 88. The error in the Medicinal Chemistry publication can be indexed by the database: a) FASTA b) PSI-BLAST c) WOMBAT d) None of above 89. Which of the following is not the program of structural conversion and cleaning: a) ChemAxon b) MOE c) 34 Sybyl d) FASTA 90. From computational point of view which system is used for drug safety development: a) DEREK b) Topkat c) MultiCASE
- 18. COMPUTER AIDED DRUG DESIGNE BP807ET d) All of above 91. Transporter classification system consists of the database: a) PubChem compound b) PubChem substance c) PubChem bioassay d) All of above 92. ..........was the lead used for development of anti-inflammatory drug Indornethacin. a. Histamine b. Serotonin c. Dopamine d. Acetylcholine 93. Bupropion was discovered through: a. Clinical observations b. Metabolic studies c. Serendipity d. Random screening 94. Fexofenadine is a metabolite of a. Diazepam b. 5-Fluorouracil c. Terfenadine d. Fluoxetine 95. Librium was discovered through: a. Clinical observations b. Metabolic studies c. Serendipity d. Random screening 96. The active principle emetine is present in: a. Ipecacuanha root b. Coca leaf c. Cinchona bark d. Belladonna leaf
- 19. COMPUTER AIDED DRUG DESIGNE BP807ET 97. Sildenafil is used for the treatment of: a. Erectile dysfunction b. Colon cancer c. Malaria d. d. Dengue 98. A second messenger molecule that turns on the enzyme guanylatecyclase, which converts guanosine triphosphate to cGMP: a. Nitric oxide b. Nitric acid c. Nitrogen d. Nitramine 99. Sildenafil inhibits which enzyme, preventing the hydrolysis of cGMP and prolonging the vasodilation effect: a. Protease b. phosphodiesterase c. DHFRase d. d. Ligase 100. The accurate structure of penicillin was elucidated by Dorothy crowfoot Hodgkin(oxford) in: a. 1894 b. 1994 c. 1944 d. 1954