Effectofmethylationonthestabilityandsolvationfreeenergyof amyloseandcellulosefragments:amoleculardynamicsstudy HaiboYu, a ManfredAmann, b TomasHansson, a,  JuttaK€ ohler, b G€ unterWich b andWilfredF.vanGunsteren a, * a Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Z€ urich, ETH H€ onggerberg, 8093 Z€ urich, Switzerland b Wacker-Chemie, Consortium f€ ur Elektrochemische Industrie GmbH, Zielstattstr 20, D-81379 Munich, Germany Received8November2003;revised6March2004;accepted3May2004 Abstract—Moleculardynamics(MD)simulationswereusedtostudythestabilityandsolvationofamyloseandcellulosefragments. Therecentlydeveloped GROMOS GROMOS carbohydrateforcefieldwasfurthertestedbysimulatingmaltose,cellobiose,andmaltoheptaose. TheMDsimulationsreproducedfairlywellthefavorableconformationsofdisaccharidesdefinedbythetorsionalanglesrelatedwith theglycosidicbondandtheradiusgyrationofmaltoheptaose.Theeffectsofmethylationatdifferenthydroxylgroupsonthestability ofamyloseandcellulosefragmentswereinvestigated.ThemethylationsofO-2andO-3reducethestabilityofasinglehelixmore thanmethylationatO-6,whilethelatterreducesthestabilityofadoublehelixmore.Solvationfree-energydifferencesbetweenthe unsubstitutedamyloseandcellulosefragmentsandthemethylatedspecieswerestudiedusingthesingle-stepperturbationmethod.It wasfoundthatmethylationatO-2hasthebiggesteffect,inagreementwithexperiment. Ó 2004ElsevierLtd.Allrightsreserved. Keywords:Computersimulation;Moleculardynamics;Amylose;Cellulose;Stability;Freeenergy;Single-stepperturbation 1. Introduction Starchandcelluloseareabundantnaturalbiomolecules connectedwithglucose.Bothofthesecompoundshave 1,4-linkedbondsbetweenglucopyranosylunitsandthey differonlyintheiranomericconfiguration.Starchcon- tainstwokindsofpolysaccharides:amyloseandamylo- pectin. Amylose, defined as a linear molecule of a-(1 fi 4)-D-glucopyranosyl units, occurs in three allo- morphs,knownastheA,B,andVforms. 1 TheAandB formsbothconsistofleft-handeddoubleheliceswithsix glucopyranosylunitsperturnandappeartodifferonly in the packing of the starch helices: the A form crys- tallizesinamonoclinicunitcell(spacegroup B2) 2 and theBforminahexagonalunitcell(spacegroup P 6 1 ). 3 V-Amylose is a generic term for amylose obtained as single helices cocrystallized with compounds such as iodine,DMSO,alcohols,orfattyacids.Althoughsuch compounds are required for formation of the V-type form,theyarenotsystematicallyincludedintheamyl- ose helix. 4;5 Sait^ oetal. 6 found that the helical confor- mations ascribed to both V- and B-types are not very different. Cellulose is a linear polymer of b-(1 fi 4)-D- glucopyranosylunitsandisthemostabundantnatural polymer on earth. Despite the considerable degree to whichcellulosehasbeeninvestigated,itsdetailedcrystal structure has not been identified with absolute clarity andisstillamatterofdebate. 7;8 Thoughambiguityex- istsregardingthedetailedatomicstructureofcellulose, experiments such as X-ray scattering and electron dif- fraction show that cellulose aggregates in a fully ex- tendedconformationtoformasheet-likestructure. The geometry of the a (axial) and b (equatorial) bondsfromcarbon1endowsamyloseandcellulosewith *Corresponding author. Tel.: +41-1-632 5502; fax: +41-1-632 1039; e-mail addresses: wfvgn@igc.phys.chem.ethz.ch; igc-sec@igc.phys. chem.ethz.ch   Presentaddress:KaroBioAB,Novum,S-14157Huddinge,Sweden. 0008-6215/$-seefrontmatter Ó 2004ElsevierLtd.Allrightsreserved. doi:10.1016/j.carres.2004.05.003 CarbohydrateResearch339(2004)1697–1709 Carbohydrate RESEARCH