Patrick: An Introduction to Medicinal Chemistry 3e

Chapter 15: Computers in medicinal chemistry

Type: multiple choice question Title: Chapter 15 - Question 01 01) hich o! the !ollo"in# operations or calculations "ould #enerally $e carried out usin# %uantum mechanics& Feedback: Quantum mechanics is used !or the calculation o! partial atomic char#es' (he other calculations or procedures are #enerally done usin# molecular mechanics Page reference: 3)*-3)+ a' ,ner#y minimisation $' Identi!yin# sta$le con!ormations -c' Partial atomic char#es d' ,ner#y calculations !or speci!ic con!ormations Type: multiple choice question Title: Chapter 15 - Question 0) 0)) hich o! the !ollo"in# so!t"are pro#rams is not used !or dra"in# ). chemical structures& Feedback: Chem3. is a #eneral molecular modellin# so!t"are pro#ram' Page reference: 3)+ a' Chem.ra" $' Chem indo" -c' Chem3. d' Isis/.ra" Type: multiple choice question Title: Chapter 15 - Question 03 03) hich o! the !ollo"in# so!t"are pro#rams is not dedicated to the creation o! 3. chemical models& Feedback: .0C1 "as one o! the early so!t"are pro#rams !or dockin# a li#and to a $indin# site' Page reference: 3)+-3)23 345 -a' .0C1 $' Alchemy c' 5yperchem d' .isco6ery 7tudio Pro Type: multiple choice question Title: Chapter 15 - Question 04 04) hich o! the !ollo"in# is associated "ith con!ormational searchin#& Feedback: (he Monte Carlo method is used in searchin# !or di!!erent con!ormations o! a molecule' 89.I is a so!t"are pro#ram used in de no6o dru# desi#n' .0C1 is used in dockin# molecules into $indin# site' CoM:A is used in 3. Q7A;' Page reference: 33+-332 a' 89.I $' .0C1 -c' Monte Carlo method d' CoM:A Type: multiple choice question Title: Chapter 15 < Question 05 05) Molecular dynamics can $e used to search !or di!!erent con!ormations o! a molecule' hich o! the !ollo"in# statements is !alse& Feedback: Measurements are calculated a!ter each !emtosecond o! mo6ement' Page reference: 335-33+ a' A 6ariety o! di!!erent con!ormations are #enerated $y =heatin#= the molecule to >001' -$' (he position and 6elocity o! each atom is measured a!ter each nanosecond o! mo6ement c' (he pro#ramme treats each atom as a mo6in# sphere d' ,ach atom is only allo"ed to mo6e a !raction o! a $ond len#th $et"een each cycle o! calculations Type: multiple choice question Title: Chapter 15- Question 0*

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0*) hich o! the !ollo"in# statements re#ardin# molecular mechanics is untrue& Feedback: Molecular mechanics in6ol6es the use o! e%uations that !ollo" the la"s o! classical physics' It treats atoms as spheres and $onds as sprin#s' Page reference: 3)* a' It treats atoms as spheres' -$' It treats $onds as ri#id !eatures' c' It is a molecular modellin# computational method' d' It uses e%uations that o$ey the la"s o! classical physics' Type: multiple choice question Title: Chapter 15- Question 0+ 0+) hich o! the !ollo"in# statements re#ardin# %uantum mechanics is untrue& Feedback: In %uantum mechanics the assumption is made that nuclei are motionless' Page reference: 3)*-3)+ a' It uses %uantum physics to calculate molecular properties' -$' It makes the assumption that nuclei are mo6in# independently o! each other c' It makes the assumption that electrons mo6e independently o! each other' d' (here are t"o $road cate#ories - ab initio and semi-empirical Type: multiple choice question Title: Chapter 15- Question 02 02) hich o! the !ollo"in# statements is true& Feedback: ,ner#y minimisation !inds a sta$le con!ormation !or a molecule3 $ut not necessarily the most sta$le con!ormation' (orsion an#les are also chan#ed' (he minimisation stops "hen there is little chan#e in ener#y $et"een one structure and the ne@t correspondin# to a sta$le con!ormation' Page reference: 3)2-3)> -a' ener#y minimisation is carried out usin# molecular mechanics $' ener#y minimisation is used to !ind the most sta$le con!ormation !or a molecule c' ener#y minimisation is carried out $y 6aryin# only $ond an#les and $ond len#ths d' ener#y minimisation stops "hen a structure is !ormed "ith a much #reater sta$ility than the pre6ious one in the process Type: multiple choice question Title: Chapter 15- Question 0> 0>) hat is meant $y a local ener#y minimum in con!ormational analysis& Feedback: (he local ener#y minimum corresponds to the !irst sta$le structure "hich is !ormed "hen ener#y minimisation is carried out' It may or may not $e the most sta$le con!ormation' (he most sta$le con!ormation o! a structure is the #lo$al ener#y minimum' Page reference: 3)2-3)>3 335 a' it is a localised re#ion o! a molecule "hich is !ree o! steric strain $' it is the most sta$le con!ormation o! a structure c' it is the initial structure that is !ormed "hen a 3. model is created3 prior to ener#y minimisation -d' it is the closest sta$le con!ormation to the startin# structure Type: multiple choice question Title: Chapter 15- Question 10 10) hat is meant $y a #lo$al ener#y minimum in con!ormational analysis& Feedback: (he #lo$al ener#y minimum corresponds to the most sta$le con!ormation o! a molecule' (he closest sta$le con!ormation to the startin# structure descri$es a local ener#y minimum "hich corresponds to the !irst sta$le structure that is !ormed "hen ener#y minimisation is carried out' Page reference: 3)2-3)>3 335 a' It is a localised re#ion o! a molecule "hich is !ree o! steric strain' -$' It is the most sta$le con!ormation o! a structure' c' It is the initial structure that is !ormed "hen a 3. model is created3 prior to ener#y minimisation' d' It is the closest sta$le con!ormation to the startin# structure' Type: multiple choice question Title: Chapter 15- Question 11

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Patrick: An Introduction to Medicinal Chemistry 3e

11) (he !ollo"in# dia#ram sho"s the ener#y o! the startin# structure prior to ener#y minimisation' the likely result o! ener#y minimisation& hat is

Feedback: ,ner#y minimisation "ould $e carried out and the structure "ould $e altered to a sta$le con!ormation' (he most sta$le con!ormation "ould $e A3 $ut there is no "ay that the so!t"are pro#ramme can predict that and so there is an e%ual likelihood o! the structure endin# up as B or A a!ter ener#y minimisation' Page reference: 335 a' ,ner#y minimisation "ould ha6e no e!!ect and the structure "ould remain at position C' $' (he structure "ould $e ener#y minimised and #i6e the most sta$le structure correspondin# to position A' -c' (he structure "ould $e ener#y minimised and #i6e a !inal structure correspondin# to either position B or A' d' ,ner#y minimisation "ould $e carried out and the !inal structure "ould correspond to position D' Type: multiple choice question Title: Chapter 15- Question 1) 1)) hich o! the !ollo"in# statements re#ardin# structural o6erlays is !alse& Feedback: (he calculation continues until the root mean s%uare distance is a minimum 6alue' Page reference: 332-340 a' (he t"o structures to $e o6erlaid should $oth $e in their acti6e con!ormations' $' 9sually speci!ic pairs o! atoms are chosen Eone !rom each molecule) to allo" the o6erlay to take place' c' (he !ittin# process normally in6ol6es $oth molecules $ein# ri#id and not chan#in# con!ormation durin# the o6erlay' -d' (he o6erlay is carried out until a ma@imum 6alue o! the root mean s%uare distance $et"een all the atom pairs is achie6ed' Type: multiple choice question Title: Chapter 15- Question 13 13) hich o! the !ollo"in# statements is true& Feedback: (he acti6e con!ormation is the con!ormation that the dru# adopts "hen it $ind to the tar#et $indin# site' Most dru#s do not react "ith their tar#et $indin# site3 other than to !orm intermolecular $onds' (here!ore3 the acti6e con!ormation does not need to $e a reacti6e con!ormation' Con!ormational analysis "ill assess the relati6e sta$ilities o! di!!erent con!ormations3 $ut it cannot predict the acti6e con!ormation' Page reference: 340 -a' (he most sta$le con!ormation o! a dru# is not necessarily the acti6e con!ormation' $' (he acti6e con!ormation is the most reacti6e con!ormation o! a structure' c' (he acti6e con!ormation is the con!ormation adopted $y a tar#et $indin# site "hen it $inds a dru#' d' (he acti6e con!ormation can $e determined $y con!ormational analysis' Type: multiple choice question Title: Chapter 15- Question 14

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14) hich o! the !ollo"in# statements is not true o! cyclic structures& Feedback: Cyclic3 ri#id structures are #enerally more di!!icult to synthesise than acyclic simpler molecules' Page reference: )10-)1)3 340-34) a' (hey are normally more ri#id than acyclic structures $' (hey ha6e !e"er possi$le con!ormations c' (hey are use!ul in determinin# the acti6e con!ormation o! a series o! related compounds -d' (hey are easier to synthesise than more !le@i$le acyclic molecules Type: multiple choice question Title: Chapter 15- Question 15 15) hat term is used to descri$e the process $y "hich dru#s are !itted into their tar#et $indin# sites usin# molecular modellin# Feedback: .ockin# is "here a molecular li#and is !itted into its $indin# site $y molecular modellin#' Page reference: 345-34> a' ,ner#y minimisation $' Con!ormational searchin# -c' .ockin# d' 06erlayin# Type: multiple choice question Title: Chapter 15- Question 1* 1*) hat term is used !or the desi#n o! a no6el dru# $ased on molecular modellin# studies o! a $indin# site Feedback: .e no6o desi#n in6ol6es the computer-aided desi#n o! a dru# $ased purely on kno"led#e o! a $indin# site3 and "ithout the $ene!it o! a lead compound' Page reference: 353-35+ a' .ru# de6elopment $' 7tructure-$ased dru# desi#n -c' De novo dru# desi#n d' .ru# optimisation Type: multiple choice question Title: Chapter 15- Question 1+ 1+) hich o! the !ollo"in# statements is !alse in de novo dru# desi#n& Feedback: I! a molecule is desi#ned to !it snu#ly3 it lea6es mo mar#in !or error' I! the molecule does not $ind as predicted3 it is unlikely to $ind at all' I! the molecule is desi#ned such that it does not !ill up the a6aila$le space3 an alternati6e $indin# mode mi#ht $e possi$le' Page reference: 353-35+ a' (he desi#n o! !le@i$le molecules is superior to ri#id ones' -$' Molecules should $e desi#ned to !it as snu#ly as possi$le into the tar#et $indin# site' c' Molecules that ha6e to adopt an unsta$le con!ormation in order to $ind should $e reFected' d' .esol6ation ener#ies cannot $e i#nored' Type: multiple choice question Title: Chapter 15- Question 12 12) hat is the so!t"are 89.I used !or& Feedback: 89.I is a so!t"are pro#ramme used !or de novo dru# desi#n' Page reference: 35+-3*1 a' .ockin# molecules into $indin# sites -$' Automated de novo dru# desi#n c' Creatin# 3. models o! molecules d' Con!ormational analysis Type: multiple choice question Title: Chapter 15- Question 1> 1>) hich o! the !ollo"in# statements is untrue "hen usin# molecular modellin# to desi#n a com$inatorial li$rary& Feedback: It is the other "ay round' (he aim is to synthesise the ma@imum num$er o! structures likely to produce the minimum num$er o! pharmacophores' Page reference: 3*1-3*) a' Pharmacophore trian#les can $e used to desi#n a li$rary'

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Patrick: An Introduction to Medicinal Chemistry 3e

-$' (he aim is to synthesise the ma@imum num$er o! structures likely to produce the minimum num$er o! pharmacophores' c' ;i#id structures should $e analysed $e!ore !le@i$le ones' d' 7tructures should only $e included in the li$rary i! they represent at least 10G additional ne" pharmacophores compared to the total represented $y structures already present in the li$rary' Type: multiple choice question Title: Chapter 15- Question )0 )0) hich o! the !ollo"in# operations or calculations "ould #enerally $e carried out usin# molecular mechanics& Feedback: Heneratin# di!!erent con!ormations is carried out usin# molecular mechanics' (he other three operations or calculations are carried out usin# %uantum mechanics' Page reference: 3)*-3)+ a' 5eat o! !ormation !or speci!ic con!ormations -$' Heneratin# di!!erent con!ormations c' Partial atomic char#es d' (ransition-state ener#ies Type: multiple choice question Title: Chapter 15- Question )1 )1) hich o! the !ollo"in# operations or calculations "ould #enerally $e carried out usin# %uantum mechanics& Feedback: (ransition state ener#ies can $e calculated usin# %uantum mechanics' (he other three operations can $e carried ut usin# molecular mechanics' Page reference: 3)*-3)+ a' 7tudyin# molecular motion' $' Heneratin# di!!erent con!ormations' c' ,ner#y minimisation' -d' (ransition-state ener#ies' Type: multiple choice question Title: Chapter 15- Question )) ))) hich o! the !ollo"in# so!t"are pro#rammes is not used !or dra"in# ). chemical structures& Feedback: 89.I is a so!t"are pro#ramme used !or de novo dru# desi#n' Page reference: 3)+3 35+ a' Chem.ra" -$' 89.I c' Chem indo" d' Isis/.ra" Type: multiple choice question Title: Chapter 15- Question )3 )3) hich o! the !ollo"in# so!t"are pro#rammes is not dedicated to the creation o! 3. chemical models& Feedback: CoM:A is a so!t"are pro#ramme used in 3.-Q7A;' Page reference: )>13 3)+-3)2 a' CAChe -$' CoM:A c' ChemB d' 7y$il Type: multiple choice question Title: Chapter 15- Question )4 )4) hich o! the !ollo"in# statements is !alse re#ardin# Monte Carlo methods o! con!ormational searchin#& Feedback: (he pro#ramme can $e used to !ind #lo$al ener#y con!ormations since a !acility is present to a6oid the structure $ein# stuck in ener#y ="ells=' At re#ular inter6als3 the pro#ramme introduces a lar#e chan#e in con!ormation to ensure that a structure is mo6ed out o! a ="ell=' Page reference: 33+-332 a' (he Monte Carlo method introduces a $ias to"ards sta$le con!ormations' -$' (he method has the dra"$ack that the structure $ecomes stuck in a local ener#y minimum ="ell= and !ails to reach the #lo$al ener#y minimum'

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Patrick: An Introduction to Medicinal Chemistry 3e

c' ,ner#ies o! randomly created con!ormations are compared3 then !urther minor modi!ications are carried out on the more sta$le con!ormations' d' ;andom con!ormations are #enerated $y carryin# out $ond rotations Type: multiple choice question Title: Chapter 15- Question )5 )5) Molecular dynamics can $e used to search !or di!!erent con!ormations o! a molecule' hich o! the !ollo"in# statements is !alse& Feedback: ,ach atom only mo6es a !raction o! a $ond len#th $e"een each round o! calculations' Page reference: 335-33+ a' A 6ariety o! di!!erent con!ormations are #enerated $y =heatin#= the molecule to >001' $' (he position and 6elocity o! each atom is measured a!ter each !emtosecond o! mo6ement' c' (he pro#ramme treats each atom as a mo6in# sphere' -d' ,ach atom is only allo"ed to mo6e a $ond len#th $et"een each cycle o! calculations'

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