Chemistry Reference
In-Depth Information
contain. the. least. hydrated. residues. while. the. most. hydrated. residues. reside. in. the.
C-terminal.tail..Unlike.the.wild-type,.there.are.no.apparent.exceptions.to.this.trend,.
even.in.the.coil/turn.connection..In.fact,.residue.38.is.still.one.of.the.least.hydrated.
even.though.it.is.in.the.coil/turn.connection..This.may.explain.the.relative.lack.of.
change.in.this.region.of.the.protein.in.the.mutant.variant..The.least.hydrated.residue.
in. the. mutant. protein. is. the. glycine. at. residue. 47. as. well. as. the. alanine. at. residue.
90,. as. expected. due. to. its. nonpolar. character.. The. most. hydrated. residue. is. again.
the. C-terminal. alanine.. While. it. is. the. most. hydrated. residue. out. of. all. the. resi-
dues.throughout.the.course.of.the.simulation.in.both.proteins,.the.average.irst.shell.
coordination.numbers.of.the.wild-type.and.A53T.mutant.synucleins.at.residue.140.
are. 5.1. and. 4.8,. respectively.. The. irst. shell. coordination. numbers. of. the. residues.
identify.which.amino.acid.residues.in.the.protein.are.the.most.soluble..The.irst.shell.
coordination. number. differences. for. residue. 140. indicate. that. the. wild-type. is. in.
fact.more.soluble.than.the.A53T.mutant..Not.only.is.the.C-terminal.less.soluble,.but.
overall.the.mutant.has.more.less-hydrated.residues.than.the.wild-type.indicating.that.
the.mutant-type.protein.is.less.soluble.than.the.wild-type..However,.this.decrease.in.
solubility.is.not.evident.at.the.point.of.mutation.because.at.residue.53,.the.coordina-
tion.is.similar.between.the.two.variants..Instead,.the.decrease.in.solubility.is.a.result.
of. the. effect. that. the. mutation. has. on. the. structure. and. dynamics. of. the. protein..
Additionally,.our.results.show.that.the.relative.hydrophobic.character.of.the.N-.and.
C-helices.and.the.hydrophilic.character.of.the.C-terminal.tail.relates.to.the.observed.
interactions.between.α-synuclein.and.the.SDS.micelles.and.lipid.bilayers.from.the.
simulations.performed.by.Perlmutter.et al..that.showed.an.increased.afinity.for.SDS.
micelles.and.lipid.bilayers.for.the.helical.regions.of.the.protein,.where.in.fact.these.
regions.imbedded.themselves.within.the.hydrophobic.core.of.the.micelles.and.the.
C-terminal.tail.remained.in.solution. 2
As.demonstrated,.the.presence.of.water.molecules.can.have.a.signiicant.impact.
on. protein. structure. and. thus. its. in. vitro. behavior.. Currently,. x-ray. and. neutron.
.diffraction.techniques.are.employed.to.obtain.structural.information.about.biomol-
ecules. and. NMR,. IR,. and. Raman. spectroscopies. are. used. to. investigate. dynamic.
structural.properties.of.biomolecules.in.aqueous.solution..While.these.experimental.
techniques. have. been. used. to. elucidate. many. structural. properties,. they. still. can-
not. capture. the. impact. of. water. beyond. the. irst. coordination. shell. on. the. protein.
structure.with.the.atomistic.details.obtained.via.dynamics.calculations..The.experi-
mental. techniques. mentioned. earlier. are. not. able. to. capture. the. dynamic. impact.
of. an. aqueous. solution. on. the. protein. structure,. especially. for. water. molecules. in.
the.second.and.third.solvation.shells.around.the.proteins..One.of.the.advantages.of.
MD. and. CPMD. simulations. is. that. these. properties. can. be. investigated. dynami-
cally. and. important. information. associated. with. the. structure,. thermodynamics,.
and.molecular.mechanisms.of.the.protein.folding.and.unfolding.can.be.determined.
simultaneously.
The.second.shell.coordination.of.water.molecules.around.the.protein.can.impact.
protein. structure. as. well,. by. interacting. with. the. irst. shell. water. molecules.. The.
second. shell. coordination. can. also. depict. the. relative. polarity. of. the. amino. acids.
within.the.protein..Residues.are.identiied.as.polar.or.nonpolar.based.on.their.side.
chains,. but. often. when. combined. into. a. large. biomolecule,. the. relative. polarity. of.
Search WWH ::




Custom Search