Nucleus Apr13.pdf

http://www.nesacs.org

April 2013 Vol. XCI, No. 8

NORTHEASTERN SECTION • AMERICAN CHEMIC

ALSO

CIET

Y

FOUNDED 1898

NESACS

Monthly MeetingThe Esselen Award Meeting at HarvardAward to František Tureček and Michael H. Gelb

Summer ScholarReportBy Morris E. Cohen, Adam Moser and BinyominAbrams, Boston University Department of Chemistry

February MeetingReportBy Jack Driscoll with photos by James Phillips

2012 GolfTournament ReportBy Amy Tapper with photos by Amy Tapper

2 The Nucleus April 2013

Call forNominationsThe 2013 James Flack Norris Awardfor Outstanding Achievement in theTeaching of ChemistryDeadline: April 15, 2013Nominations are invited for the 2013James Flack Norris Award, which con-sists of a certificate and an honorariumof $3,000 and is given annually by theNortheastern Section (NESACS). Thepresentation will take place at a cere-mony and dinner in November 2013,and will include a formal address bythe awardee. The Award was estab-lished in 1950 by NESACS to honorthe memory of James Flack Norris(1871-1940), a professor of chemistryat Simmons College and M.I.T., chairof NESACS in 1904, and ACS Presi-dent in 1925-26.

Nominees should have served withspecial distinction as teachers of chem-istry at any level: secondary school,college, and/or graduate school. Withthe presentation of the first Award in1951, awardees have included manyeminent teachers at all levels whoseefforts have had a wide-ranging effecton chemical education. The recipientwill be selected from an internationallist of nominees who have served withspecial distinction as teachers of chem-istry with significant achievements.

A nomination in the form of a let-ter should focus on the candidate’scontributions to and effectiveness inteaching chemistry. The nominee’scurriculum vitae should be includedand, where appropriate, a list of hon-ors, awards, and publications related tochemical education. Seconding lettersmay also be included; these shouldshow the impact of the nominee’steaching for inspiring colleagues andstudents toward an active life in the

chemical sciences, and attest to theinfluence of the nominee’s other activi-ties in chemical education, such astextbooks, journal articles, or otherprofessional activity at the local,national, and international level.

The nomination materials shouldconsist of the primary nomination let-ter, supporting letters, and the candi-date’s curriculum vitae. Reprints orother publications should NOT beincluded. The material should notexceed thirty (30) pages, and should besubmitted electronically in Adobe PDFformat through April 15, 2013 to Ms.Anna Singer, NESACS AdministrativeSecretary <[email protected]>.For more information about the Award,see http://www.nesacs.org/awards_nor-ris.html>.

Questions about the Award or thenomination process should be directedto the Chair of the Norris Award Com-mittee, Professor Mary Shultz,<[email protected]>. u

http://www.nesacs.org/awards_norris.html

The Nucleus April 2013 3

The Nucleus is published monthly, except June and August, by the Northeastern Section of the AmericanChemical Society, Inc. Forms close for advertising on the 1st of the month of the preceding issue. Textmust be received by the editor six weeks before the date of issue.Editor: Michael P. Filosa, Ph.D., ZINK Imaging, Inc., 16 Crosby Drive, Building 4G,

Bedford, MA 01730 Email: Michael.filosa(at)zink.com; Tel: 508-843-9070Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273,

Sheila E Rodman, Email: serodman(at)hotmail.com, Mindy Levine, 516-697-9688, mindy.levine(at)gmail.com

Board of Publications: Mary Mahaney (Chair), Mindy Levine, Vivian K. Walworth, James PhillipsBusiness Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050,

Email: Manager-vincegale(at)mboservices.net; Tel: 781-837-0424Contributing Editors: Morton Hoffman, Feature Editor; Dennis Sardella, Book Reviews Calendar Coordinator: Sheila Rodman, email: serodman(at)hotmail.comPhotographers: Morton Z. Hoffman and James PhillipsProofreaders: Donald O. Rickter, Vivian K. Walworth, Mindy Levine Webmaster: Roy HagenCopyright 2013, Northeastern Section of the American Chemical Society, Inc.

The Northeastern Section of the AmericanChemical Society, Inc.Office: Anna Singer, 12 Corcoran Road,Burlington, MA 01803(Voice or FAX) 781-272-1966.e-mail: secretary(at)nesacs.orgNESACS Homepage:http://www.NESACS.orgOfficers 2013ChairLiming Shao158South Great RoadLincoln, MA 01773limingshao(at)comcast.netshao(at)fas.harvard.edu781-518-0720Chair-ElectCatherine CostelloBoston University School of Medicine670 Albany Street, room 511Boston, MA 02118-2646Cecmsms(at)bu.eduImmediate Past ChairRuth TannerOlney Hall 415BLowell, MA 01854University of Mass LowellRuth_Tanner(at)uml.edu978-934-3662Secretary:Michael SingerSigma-Aldrich3 Strathmore Rd, Natick, MA 01360774-290-1391, michael.singer(at)sial.comTreasurer:James Piper19 Mill Rd, Harvard, MA 01451978-456-3155, piper28(at)attglobal.netAuditor:Anthony RosnerArchivistTim FrigoTrustees:Peter C. Meltzer, Esther A. H. Hopkins,Michael E. StremDirectors-at-LargeDavid Harris, Stephen Lantos, James Phillips,Ralph Scannell, Mary Burgess, John BurkeCouncilors Alternate CouncilorsTerm Ends 12/31/2013Alfred Viola Mark FroimowitzMichael Singer Sophia R. SuRobert Lichter Kenneth C. MattesMary Shultz Tim FrigoLeland L. Johnson, Jr. Mukund ChorghadeTerm Ends 12/31/2014Katherine Lee C. Jaworek-LopesMichael P. Filosa Lawrence ScottDoris Lewis Andrew ScholteMorton Z. Hoffman Raj RajurPatrick Gordon John PodobinskiMary Burgess Stuart LevyTerm Ends 12/31/2015Catherine E. Costello Marietta SchwartzRuth Tanner JerryJasinskiDorothy J. Phillips Stephen LantosMichaeline Chen Norton P. PeetJackie O’Neil Wilton Virgo

ContentsCall for Nominations____________________________________22013 James Flack Norris Award for Outstanding Acheivement in the Teaching of Chemistry

February Monthly Meeting Report _________________________4By Jack Driscoll, NESACS Public Relations Chair. Photos by James Phillips.(Cover photo by Morton Z. Hoffman).

Monthly Meeting _______________________________________5Esselen Award Meeting at the Harvard Faculty Club and Pfizer Lecture Hall,Award to František Tureček and Michael H. Gelb

8th Annual NESACS Golf Tournament Report _________________ 6By Amy Tapper with photos by Amy Tapper

9th Annual NESACS Golf Tournament Announcement___________7

Summer Scholar Report _________________________________8Towards an All-Atom Model for m-Poly(phenylene ethynylene) Class ofFoldamers using theCHARMM27 Force Field: Structure and Unfolding Pathway of Foldamers of Various Lengths Morris E. Cohen, Adam Moser, and Binyomin Abrams, Department of Chemistry,Boston University, Boston MA

Cambridge Science Festival Annoucement__________________12

NESACS at Fenway Park-May 10, 2013____________________16

Cover: A photo from the February Meeting at Northeastern University, 140 TheFenway. Pictured (L-R) are Liming Shao, 2013 NESACS Chair; February’sspeaker, Jeannette Brown, Merck retired; and Prof. Patricia Mabrouk, North-eastern University, NESACS WCC Chair. Photo by Morton Z. Hoffman.

Editorial Deadlines: Summer 2013 Issue: June 15, 2013 September 2013 Issue: July 15, 2013

All Chairs of standingCommittees, the editor of THE NUCLEUS, and the Trustees of SectionFunds are members of theBoard of Directors. AnyCoun cilor of the American Chemical Soci-ety residing within the section area is an exofficio member of the Board of Directors.


The February monthly meeting ofNESACS was held at NortheasternUniversity at 140 The Fenway acrossfrom the Museum of Fine Arts. Thebuilding was formerly the site of theForsythe Institute. Parking was diffi-cult as a result of the recent blizzard inBoston’s very snowy February. Ourguest speaker was Jeanette Brown, for-merly an organic chemist for Ciba-Geigy and Merck, where she(http://www.thehistorymakers.com/biography/jeannette-brown-42) developeddrugs for diseases such as tuberculosis

and coccidiosis. The location of themeeting was arranged by Prof. PamMabrouk of Northeastern University.

After her industrial career,Jeanette was appointed chairperson ofthe Project SEED Committee for theAmerican Chemical Society. She alsoserved on the faculty of the New Jer-sey Institute of Technology (NJIT) as avisiting professor of chemistry and afaculty associate. She was interested inscience education and biographies ofAfrican American chemists. She went

on to publish her own book in 2011,entitled, “African American WomenChemists,” which was her topic for ourFebruary meeting of NESACS. Thisbook was published by Oxford Univer-sity Press and is readily available atretailers such as Amazon.

The monthly meetings typicallyinvolve a board meeting from 4:30-5:30pm followed by an hour of net-working with hor d’oeuvres andbeverages, followed by dinner andcapped with a talk by an interesting

Corporate Patrons $2000 - or moreAstraZeneca PharmaceuticalsEisai PharmaceuticalsEMD SeronoGenzyme Corp.Johnson MattheyMerck & Co.NovartisPfizer Inc.Schering Corp.Strem Chemicals, Inc.Vertex Pharmaceuticals$1000-$1999Boehringer IngelheimGlaxoSmithKlineIrix PharmaceuticalsLyophilization Services of NESundia MeditechYes Bank$300-$999Cambridge Major LabsGirindusMerrimack ConsultantsOrganixPCI SynthesisSigma AldrichWaters Corp.Wilmington PharmaTech

February Monthly MeetingBy Jack Driscoll, Public Relations Chair, NESACS

continued on page 13

Ruth Tanner, NESACS Immediate Past Chair (l),Jeanette Brown, Liming Shao, NESACS 2013Chair (Photo by James Phillips)

Jack Driscoll, PR Chair NESACS, PatriciaMabrouk, Woman Chemists Committee Chair,NESACS (Photo by James Phillips)

Dorothy Phillips (l) and Jeanette Brown withher new book- (Photo by James Phillips)


AbstractThe Chemistry of Next GenerationNewborn ScreeningNewborn screening of inborn errors ofmetabolism is an important moderncomponent of public health that allowsdetection of several genetic disordersenabling the start of early treatment ofaffected children. We have developednew chemical methods for rapid andreliable measurements of enzymeactivities that are indicative of genetic

defects associated with lysosomal stor-age disorders, porphyrias, and congeni-tal disorders of glycosylation. The firstpart of the lecture will deal with thetechnique of affinity capture-releasemass spectrometry and its applicationsto clinical enzymology and pro-teomics. The second part will addressthe detection by tandem mass spec-trometry of lysosomal storage disor-ders in dried blood spots and recentprogress in multiplexing our analyticalmethods for large-scale newbornscreening. u

Monthly MeetingThe 932nd Meeting of the Northeastern Section of theAmerican Chemical SocietyThursday, April 4, 2013Harvard University, Cambridge, MAHarvard Faculty Club, 20 Quincy Street

4:30 pm Board Meeting

5:30 pm Social Hour

6:30 pm Dinner

8:15 pm Award Meeting, Mallinckrodt Building, 12 Oxford St.Pfizer Lecture Hall (MB23), ground floor.Dr. Liming Shao, NESACS Chair, presidingWelcome – Dr. Anna Sromek, Chair, Esselen Award CommitteeThe Esselen Award - Dr. Myron S. Simon, Founding Member of the

Esselen Award CommitteeIntroduction of the Award Recipients – Dr. Paul B. Hopkins,

Chair, Department of Chemistry, University of Washington.Presentation of the Award - Gustavus J. Esselen, IVMichael H. Gelb, Harry and Catherine Jaynne Boand Professor of

Chemistry, and František Tureček, Professor of Chemistry, Uni-versity of Washington.

Lecture: The Chemistry of Next Generation Newborn ScreeningDinner reservations should be made no later than noon, Thursday, March 28.Reservations are to be made using PayPal services: http://acssymposium.com/paypal.html. Select pay with credit or debit card optionand follow the additional instructions on the page. Members, $30; Non-mem-bers, $35; Retirees, $20; Students, $10. Reservations for new members and foradditional information, contact the secretary Anna Singer at (781)272-1966between 9am and 6pm or e-mail at [email protected]. Reservations notcancelled at least 24 hours in advance must be paid.THE PUBLIC IS INVITEDFree Parking in the Broadway Street garage (3rd level or higher), enter fromCambridge St. via Felton St.

Biographies Dr. František Tureček

Dr. František Tureček was born inPrague, Czechoslovakia, where hereceived a Ph.D. in organic chemistryfrom Charles University in 1977. In1987 he and his family left Czechoslo-vakia, and, after spending a year in arefugee camp, they moved to theUnited States, where he joined FredMcLafferty at Cornell University. In1990 he joined the faculty of theChemistry Department at University ofWashington, Seattle. His researchinterests have been in the chemistry ofhighly reactive molecules (enols,sulfenic acids), hypervalent radicals,nucleobase radicals related to DNAdamage, and peptide radicals andcation-radicals. His other interestsinclude mass spectrometric instrumen-tation, gas-phase ion chemistry, ion-surface interactions (soft and reactivelanding), and applications to pro-teomics, clinical analysis, and newbornscreening. He is author of >370 scien-tific papers, three books, and severalpatents. Among his recent awards arethe P. B. Hopkins Faculty Award, theCzech Head-Patria Science Prize, theJohannes Marcus Marci SpectroscopyAward, and the Thomson Medal of theInternational Mass Spectrometry Fed-eration. Michael H. GelbProfessor Michael H. Gelb is the Harryand Catherine Jaynne Boand EndowedProfessor of Chemistry and Biochem-istry at the University of Washington inSeattle. Gelb received his B.S. degreefrom the University of California,Davis and his Ph.D. with Stephen G.Sligar at Yale University on aspects ofthe catalytic mechanism of cytochromeP450. Granted an American Cancer



In 2012, the 8th annual NESACS GolfTournament was again held at Wedge-wood Pines Country Club in Stow,MA. A total of 62 players participatedin the scramble format tournament.The afternoon began with a box lunchfollowed by a shotgun start at 1 PM.The lunchtime is a good opportunityfor players to practice their putting andchipping as well as to network withcolleagues who travel from all over theUS to attend this annual event. Afterthe tournament, a cocktail hour is held,followed by a buffet dinner and awardsceremony.

This year there was a three-way tiefor first place with the winning score of64 (8 shots under par). The winnerswere then determined by their score onthe hardest holes (or highest handicapholes). The golfers on the first-placeteam were Damon Abernathy, NickFudula, Andrew Morbey, and Ed Mor-bey. The golfers on the second-placeteam were Tae Cho, David Akeson,Dav Terro, and Sohan Abraham. The

golfers on the third place team wereStu Needleman, Paul Defino, NathanBarashansky, and Kevin Duffield.Prizes were also given for the longestdrive and closest to the pin for bothmen and women. The men’s long drivewas won by John Green and the ladiesby Angeles Dios. The men’s closest-to-the-pin was won by Doug Saffran andthe ladies’ by Cassandra Celatka.

We are extremely grateful to thesponsors of this tournament. All pro-ceeds from this tournament supportNESACS programs. Over the past sev-eral years and again in 2012, our high-est donor was the LyophilizationServices of New England (LSNE)(http://www.lyophilization.com). Our other generous sponsors who par-ticipated were: • Aptuit (http://www.aptuit.com)• Cambridge Major Laboratories

(http://www.c-mlabs.com)• Emerson Resources

(http://www.emersonresources.com)

• IRIX Pharmaceuticals(http://www.irixpharma.com)

• Johnson Matthey Pharma Services(http://www.jmpharmaservices.com).

Please visit their websites to investi-gate their services and capabilities

We are looking forward to the 9th

annual tournament, to be held onAugust 5, 2013 at the Kernwood CC inSalem, MA. u

NESACS 8th Annual Golf TournamentBy Amy Tapper (Photos by Amy Tapper)

First-place team (L-R)- Damon Abernathy,Edward Morbey, Andrew Morbey, Nick Fudalawith tournament co-chair Harry Mandeville.

Second-place team- Tae Cho(R), David Akeson,Dav Terro, and Sohan Abraham(L)

Third-place team (L-R) Paul Defino, Stu Needle-man, Kevin Duffield, Nathan Barashansky

Closest to the pin Doug Saffran with HarryMandeville photos continued on page 11

9th Annual NESACS Scramble Golf Tournament2013 Tournament Co-Organized with PCI Synthesis

Kernwood Country Clubwww.kernwoodcc.org

Salem, MAAugust 5, 2013

BBQ Lunch followed by a Shot Gun Start at 1 PMBuffet Dinner and Awards Immediately Following

Cost: $170 per golferFee Includes:Greens fee, Cart

Full BBQ lunch, snacks and drinks on the course, passed appetizers, and full buffet dinner with carving stations

Prizes include longest drive, closest to the pin, first, second, and third place teams

Hole Sponsorships are available at the suggested levels:

$2500 Boron$2000 Osmium$1500 Sulfur$1000 Tritium$500 Oxygen$300 Nitrogen

Please note: hole sponsorships are very important. All proceeds support NESACS pro-grams

Registration: contact Harry Mandeville at [email protected]. Please include allgolfers’ names and e-mail addresses. Payment: by check only. Please send your check to:

Harry Mandeville7 Pillings Pond RoadLynnfield, MA 01940



AbstractAn all-atom model for the m-Poly(phenylene ethynylene)(mPPE) class of foldamers was developed for theCHARMM27 force field. The folding behavior of mPPEs ofdifferent residue lengths with triethylene glycol exohelicalside chains in explicit water were studied by all-atommolecular dynamics simulations with the CHARMM27force field. mPPEs were studied in both the helical andextended conformations in water to find the minimumenergy structures. The unfolding pathway and free energylandscapes of the foldamers were probed using metadynam-ics, in which the folded state was determined to be 8.5 and16.3 kcal · mol−1 more favorable in implicit solvent andexplicit solvent, respectively.IntroductionBiological macromolecules, such as proteins, lipids, andDNA self-assemble into compact solution structures.1

Folded conformations are determined by temperature,hydrogen bonding, and van der Waals interactions. Due tothe prevalence of folding in bio-macromolecules, a deepunderstanding of the folding process is of particular impor-tance.2 Consequently, significant work has been done tounderstand the fundamental science behind the foldingprocess.3 Because of the complex nature of proteins andother bio-macromolecules, compounds that mimic the wayproteins behave have been sought out.4 Nonetheless, despiteα-helices being one of the most common protein structures,5there exist relatively few synthetic molecules that mimic anα-helix.1 This has led to the development of m-Poly(pheny-lene ethynylene) or mPPEs,6 oligomers that fold using non-covalent interactions between atoms to adopt a helicalstructure that is more thermodynamically favored in solu-tion. J. Moore and others6–10 have shown that mPPEs withester side chains and a residue length of 12 or more adopt aspecific α-helix conformation in acetonitrile and water.

mPPEs have been both synthesized7,11,12 and mod-eled,13–15 but few are water soluble, which presents a signifi-cant limitation on their application to biological systems.9,16

Both Saven13 and Sen17 have independently shown that thefolded α-helix conformation is a minimum energy structure.Bruce and others12, 18–20 have shown that mPPEs with smallexohelical side chains ( COOMe, CONH2 , etc.) prefer afolded conformation over an extended conformation. Addi-tionally, Elmer 21 has shown that mPPEs can get trapped inmisfolded states during the folding process, similar to thatof proteins.

In this study, we examine the effect of residue length onthe folding propensity of mPPE with triethylene glycol ester

side chains (COOTg) in both explicit and implicit solvent.Moore has previously shown experimentally that an mPPEwith residue length of eight will not fold, and a residuelength of ten will form a semi-folded state.10 Additionally,the free energy landscape of unfolding was investigatedusing metadynamics, an accelerated sampling method usedto study free energy surfaces and force systems out of localminima in molecular dynamics simulations.22

Parameterization of mPPE and Simulation Details

ParameterizationThe potential energy term for the CHARMM force

field23 is given by:

Figure 1: Structure of mPPE monomer. C8 is connected to C2 of the fol-lowing unit. 1, 2, and 3 have monomer lengths of 8, 10, and 12, respec-tively. Triethylene glycol (Tg) side chains were used in this study.

Figure 2: Structure of tolane. The potential for the dihedral angle φbetween the two benzene rings was calculated by Okuyama experimentallyto be 0.6 kcal·mol−1.29

Table 1: Comparison of HF charges to the charges used for mPPE (atomslabeled in Figure 1)

Summer Scholar ReportTowards an All-Atom Model for m-Poly(phenylene ethynylene) Class of Foldamers using theCHARMM27 Force Field: Structure and Unfolding Pathway of Foldamers of Various LengthsMorris E. Cohen, Adam Moser,† and Binyomin Abrams,* Department of Chemistry, Boston University, Boston MA*To whom correspondence should be addressed. E-mail: [email protected]† Current address: Loras College, Dubuque, IA

where the force constants Kb, Kθ, KUB, Kφ, Kψ are the bond,angle, Urey-Bradley, dihedral, and improper dihedral forceconstants, respectively; b, θ , s, φ , ψ are the bond length,bond angle, Urey-Bradley distance, dihedral angle, andimproper dihedral, respectively.

Force field parameters for 3 (mPPE 12-mer, Figure 1)were either obtained from analogous residues in theCHARMM27 force field24 or were developed to fit experi-mental results and quantum mechanical calculations. Thetriethylene glycol side chain parameters were taken from theCHARMM ether force field. 25 The ester functional groupparameters were taken from the CHARMM lipid parametersfor deoxylysophosphatidyl-choline (LPPC).26 The triplebond carbon parameters were taken from the CGenFFparameters of 2-butyne.27 The benzene carbons and hydro-gens were matched to the benzene parameters of phenylala-nine.24 The missing charges (C2, C4, C6-8, Figure 1) werecalculated using Gaussian0928 using HF/631G** basis setand fit to ensure charge neutral groups. The parameters forthe dihedral, φ, between the two benzene planes (Figure 2)were derived from Gaussian09 HF/631G** calculations, andusing experimental data of tolane,29 to produce the correctrotational potential energy surface. The ab initio torsionalpotential energy surface was obtained from a 90˚ rotationalscan in 10◦ increments due to the periodicity of the potentialenergy surface. Parameters were then created Kφ , n, and δto match the potential energy surface. The best-fit parame-ters were determined to be a force constant Kφ = 0.06 kcal ·mol−1 · rad−2, periodicity n = 2, and δ = 180˚.Simulation Details

Initial helical configurations of mPPE were generatedusing the CHARMM36 package and the new mPPE param-eters. Explicit solvent simulations had one mPPE solvatedin TIP3P water in truncated octahedra (8469 TIP3P watersand side of length of 80 Å for 3). Equilibration runs (500 ps)and production runs (10-50 ns) were performed using 1 fsintegration timesteps using the NAMD2 package.30 TheNPT ensemble was generated using Langevin piston methodat 1 atm with a piston temperature of 300 K, a piston periodof 200 fs, and a damping time constant of 100 fs. Electro-statics were treated using Particle Mesh Ewald. Non-bondedinteractions were calculated using a switching functionbetween 12 and 14 Å.

For implicit solvent simulations, Generalized BornImplicit Solvent modeling water as a dielectric continuumwith a dielectric of 78.5 was used. Equilibration runs (1 ns)and production runs (100 ns) were performed using 1 fsintegration timesteps using the NAMD2 package30 withlangevin temperature control. An alpha cutoff of 16 wasused for calculating Born radius. Non-bonded interactionswere calculated using a switching function between 16 and18 Å.

Results and Discussion

StructureIn explicit solvent, mPPEs 1-3 remained in the folded

conformation throughout simulations up to 50 ns, and forsimulations of 100 ns in implicit solvent. The time evolutionof Rg for 3 is shown in Figure 3 (explicit solvent) and Fig-


Summer Scholarcontinued from page 8

Figure 3: Time evolution of Rg for 3 in explicit solvent beginning in thefolded conformation (red) and extended-coil conformation (green). Theextended-coil conformation collapses into a misfolded knotted structurethat is not escaped for the rest of the simulation.

Table 2: Structural conformation data for mPPEs of different oligomerlengths. Rg refers to radius gyration of the mPPE backbone. The pitchrefers to the average distance between the planes of benzenes six residuesapart


Figure 4: Time evolution of Rg for 3 in implicit solvent beginning in thefolded conformation (red) and extended-coil conformation (green). Theextended-coil conformation collapses into a semi-folded structure after 2ns and eventually collapses into a misfolded state, which it does notescape.


ure 4 (implicit solvent). Rg remained constant at a value ofnearly 6.5 Å (Table 2) for all three foldamers, in bothexplicit and implicit solvents, which indicates a strongfavoring of the folded structure. The helix pitch, measuredas the average distance between the planes of benzenes sixresidues apart, was determined to be 3.42 Å, which is con-sistent with the experimental value of 3.5 Å.10

Simulations of 3 beginning in a random coil show asharp decrease in Rg at 12 ns in explicit solvent, which cor-responds to a collapse in structure from an extended-coilinto a misfolded structure (Figure 3). In implicit solvent, asemi-folded structure was achieved after 2 ns (Figure 4).Furthermore, a misfolded structure, with Rg equivalent tothe folded structure, occurs at 30 ns and persists for the

remainder of the 100 ns simulation. While Rg of 3 inimplicit solvent beginning in an extended-coil eventuallyreaches that of the folded structure, examination of thestructure shows a compressed, misfolded structure. Metadynamics

The free energy associated with uncoiling of the mPPEswas determined using metadynamics31 where a history-dependent bias potential is used to fill the free energy sur-face (FES) over time and allow efficient sampling of theFES. The form of the bias potential on a collective variableξ is given as:

where W is the gaussian hill height and δ is the hill width. Rgwas chosen as the collective variable to study the unfoldingpathway (W = 0.1 kcal · mol−1, δ = 0.3 Å, and gaussianswere added every 1000 steps).

The folded conformations were the global minima in

the free energy profiles along Rg, in both explicit andimplicit solvent, which is consistent with the experimentalresults (Figure 5). In explicit solvent, the folded conforma-tion was found to be 16.3 kcal · mol−1 more stable than theextended-coil conformation. As expected, the implicit sol-vent model leads to increased sampling of the non-nativestates32 and the free energy of unfolding (8.5 kcal · mol−1 for3 in implicit solvent) is significantly lower than that pre-dicted by the explicit model. Furthermore, the minimumobserved in implicit solvent was located at a slightly largerradius of gyration (Rg = 6.8) than in explicit solvent (Rg =6.4), due to the fact that the helix in implicit solventachieved a slightly larger helix radius before unfolding.Additionally, the broadening of the implicit solvent freeenergy well is due to the prevalence of thermodynamically-favorable semi-folded structures that occur with Rg near 7.Nonetheless, there is good qualitative agreement betweenthe results for the unfolding pathway generated in implicitand explicit solvent.Conclusions

In this paper, the parameterization of the mPPE class offoldamers is discussed. The new CHARMM parameters formPPE have been shown to correctly reproduce the experi-mentally determined folded structure for oligomers of 8, 10,and 12 monomers. Simulations on these mPPEs starting inthe folded conformation remain folded in both implicit andexplicit solvent. Additionally, mPPEs starting in theextended-coil conformations collapse into mis-folded andsemi-folded conformations, which are more stable than theextended-coil conformations. Free energy sampling frommetadynamics further confirms that the folded conformationis preferred over the extended state by 8.5 and 16.3kcal·mol−1 in implicit and explicit solvent, respectively. Asexpected, implicit solvent simulation underestimate the freeenergy of folding.

Our results indicate that the mPPE model correctly pre-dicts the equilibrium structure of the native state foroligomers of length 8-12 monomers and provides a freeenergy of unfolding that is consistent with the experimentalresults in acetonitrile. The relative free energies of unfoldingof different length oligomers, and the relative free energiesof unfolding in different solvents, deserve a separate study.Acknowledgementsx0

The authors gratefully acknowledge the support of theBoston University Undergraduate Research OpportunitiesProgram, the Northeastern Section of the American Chemi-cal Society, the Boston University Scientific Computing andVisualization Group, and the National Science Foundation.MC acknowledges the James Flack Norris and TheodoreWilliam Richards Undergraduate Summer Scholarship.References(1) Guichard, G.; Huc, I. Chem. Commun. 2011, 47, 5933–5941. (2) Vendruscolo, M.; Zurdo, J.; MacPhee, C. E.; Dobson, C. M.

Phil. Trans. R. Soc. Lond. A. 2003, 361, 1205–1222. (3) Dobson, C. M. Nature 2003, 426, 884–890. (4) Hecht, S., Huc, I., Eds. Foldamers: Structure, Properties,


Figure 5: Potential of mean force for 3 calculated using metadynamics onRg collective variable, in explicit (red) and implicit (green) solvent. Thefolded state is found to be 8.5 kcal · mol−1 (implicit solvent) and 16.3 kcal ·mol−1 (explicit solvent) more stable than the extended conformation.



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(6) Nelson, J. C.; Saven, J. G.; Moore, J.S.; Wolynes, P. G. Science 1997, 277,1793–1796.

(7) Prince, R. B.; Barnes, S. A.; Moore,J. S. J. Am. Chem. Soc. 2000, 122,2758–2762.

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(9) Stone, M. T.; Moore, J. S. Org. Lett.2004, 6, 469–472.

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(12) Nguyen, H. H.; McAliley, J. H.;Bruce, D. A. Macromolecules 2011,44, 60–67.

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(16) Arnt, L.; Tew, G. N. Macromolecules2004, 37, 1283–1288.

(17) Sen, S. J. Phys. Chem. B 2002, 106,11343–11350.

(18) Adisa, B.; Bruce, D. A. J. Phys.Chem. B 2005, 109, 7548–7556.

(19) Adisa, B.; Bruce, D. A. J. Phys.Chem. B 2005, 109, 19952–19959.

(20) Nguyen, H. H.; McAliley, J. H.; III,W. R. B.; Bruce, D. A. Macromole-cules 2010, 43, 5932– 5942.

(21) Elmer, S.; Pande, V. S. J. Phys.Chem. B 2001, 105, 482–485.

(22) Laio, A.; Gervasio, F. L. Rep. Prog.Phys. 2008, 71, 126601.

(23) Brooks, B. R. et al. J. Comput.Chem. 2009, 30, 1545–1614.

(24) MacKerell, A. D. et al. J. Phys.Chem. B 1998, 102, 3586–3616.

(25) Vorobyov, I.; Anisimov, V. M.;Greene, S.; Venable, R. M.; Moser,A.; Pastor, R. W.; Alexander D.MacKerell, J. J. Chem. Theory Com-put. 2007, 3, 1120–1133.

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2012 Golf Winners continued from page 6

Closest to the pin Cassandra Celatka Longest drive- John Green Longest drive- Angeles Dios

Cambridge Science FestivalNortheastern Section of the American Chemical Society

http://www.nesacs.orgThe Cambridge Science Festival, the first of its kind in the United States, is an annual tenseries of daylong events based on science, technology, engineering & math (STEM). TheFestival makes science accessible, interactive and fun! The schedule of events for April 13-21, 2013 is: http://cambridgesciencefestival.org/2013Festival/2013ScheduleOfEvents.aspx

A signature event is the Science Carnival on Sat. April 13, 2013. Schools supporting theevent include MIT, Harvard, Suffolk University, Northeastern University and many more. TheAmerican Chemical Society (ACS), the world’s largest scientific society, with 164,000 mem-bers, and the Northeastern Section of the ACS will be represented.

The Cambridge Science Festival is organized and run by the MIT Museum. The MIT Museumalso has a program called “Science on the Streets”. This program uses researchers andinnovators to engage audiences with their love of STEM to kids, families and adults attend-ing cultural and community events throughout Massachusetts. Volunteers are needed.

Prepared byDr. Jack Driscoll, Chair, Public Relations, Northeastern Section of the ACS.


12:00pm - 4:00pm

Cost: Free

Come one, come all!! The annual Science Carnival of CSF iskicking off the Festival yet again this year, Bring curious mindsof all ages! Check back for updates soon!


speaker. I am always amazed at whatcan get accomplished during the net-working session. If you want to getinvolved, why not come to a monthlymeeting. Meetings are most often heldthe second Thursday of each month.You can find the time, date and loca-tion in The Nucleus or on the NESACSwebsite (nesacs.org). We have somevery interesting industrial and aca-demic people at these meetings. Wealso have many active committees andneed more volunteers. u

February Meetingcontinued from page 4

D I R E C T O R Y

SERVICES

Apr 23Prof. Sam Thomas (Tufts University)Brandeis, Gerstenzang 121 4:00 pmProf. David Moore (Lehigh University) “Using cryogenic spectroscopy to elucidateinteractions of reactant molecules withnanocatalyst materials”Tufts, Room P-106 4:30 pmProf. Michael Jennings (University of Alabama)Total Syntheses of α-and β-C-glycoside NaturalProducts via Oxocarbenium CationsUNH Room N104 (formerly L103)11:10 amProf. David Moore (Lehigh University)“Using cryogenic spectroscopy to elucidateinteractions of reactant molecules withnanocatalyst materials”Tufts, Room P-106 4:30 pm

Apr 24Prof. Ted Betley (Harvard University)MIT, 6-120 4:15 pm

Apr 25Prof. Hannah Sevian (Boston University)“Developing a Learning Progression onChemical Design”UNH Room N104 (formerly L103) 11:10 amProf. Matthew S. Sigman (University of Utah)Prof. Jonathan Ellman (Yale University)MIT, 6-120 4:00 pm

Apr 26Prof. Melanie Sanford (University of Michigan)WPI, Gateway Park, Rm. 100212:00 Noon

Apr 29Prof. Eric Ferreira (Colorado State University)Brandeis, Gerstenzang 121 4:00 pmProf. Wilfred A. van der Donk (University ofIllinois at Urbana-Champaign)“Phosphate Biosynthesis: A Treasure Trove forNovel Chemistry”MIT, 56-114 4:00 pm

Apr 30Prof. Eric Ferreira (Colorado State University)Boston College, Merkert 1304:00 PMProf. Basar Bilgicer (Notre Dame University)“Multicomponent molecular design fortherapeutic applicationsTufts, Room P-106 4:30 pmProf. Elizabeth M. Nolan (MIT)UNH Room N104 (formerly L103) 11:10 am

Notices for The NucleusCalendar of Seminars should be sent to:Sheila E Rodman, email:serodman(at)hotmail.com

Calendarcontinued from page 16

Society postdoctoral fellowship, hethen investigated mechanism-basedinactivators of serine proteases anddeveloped fluorinated ketones as tight-binding inhibitors of several classes ofproteases working with Robert H.Abeles at Brandeis University.

His current research interestsinclude: 1) Studying the function andregulation of a group of enzymescalled phospholipase A2 that areinvolved in lipid mediator biosynthesisrelated to inflammation; 2) Anti-malaria and anti-trypanosome drugdiscovery; 3) New technology for thenewborn screening of enzyme defi-ciency diseases including lysosomalstorage diseases.

He is author of >350 scientificpapers and several patents. Among hisawards are the P. B. Hopkins FacultyAward, the Medicines for Malaria Ven-ture Project of the Year Award, The ICIChemicals Excellence in ChemistryAward, The Pfizer Award from theAmerican Chemical Society, and theAlfred P Sloan Fellowship Award. Hewas recently elected as a Fellow of theAmerican Association for the Advance-ment of Science. u

BiographiesMichael H. Gelb continued from page 5

http://www.nesacs.org


B U S I N E S S D I R E C T O R Y

SERVICESSERVICESSERVICES


CAREER SERVICESSERVICES

B U S I N E S S D I R E C T O R Y

SERVICES

Index of AdvertisersAsisChem, Inc. ....................14Boston College ....................15ChemDev Solutions ..............4Eastern Scientific Co.............6Front Run OrganX, Inc........14Huffman Laboratories, Inc. .14Mass-Vac, Inc.......................11Micron Inc. ..........................14New Era Enterprises, Inc.....14NuMega Resonance Labs....14Organix, Inc.........................14PCI Synthesis ......................13PolyOrg, Inc. .......................15Rilas Technologies, Inc. ......15Robertson Microlit Labs. ....14Waters Corporation .............15

Check the NESACS home pagefor late Calendar additions:http://www.NESACS.orgNote also the Chemistry Department webpages for travel directions and updates.These include:http://www.bc.edu/schools/cas/chemistry/semina

rs.htmlhttp://www.bu.edu/chemistry/seminars/http://www.brandeis.edu/departments/chemistry/

events/index.htmlhttp://www.chem.harvard.edu/courses/seminars.

phphttp://chemcalendar.mit.edu/index.phphttp://chem.tufts.edu/seminars.htmlhttp://engineering.tufts.edu/chbe/newsEvents/se

minarSeries/index.asphttp://www.chem.umb.eduhttp://www.umassd.edu/cas/chemistry/http://www.uml.edu/Sciences/chemistry/Seminar

s-and-Colloquia.aspxhttp://www.unh.edu/chemistry/events

Apr 01Prof. Douglas Stephan (University of Toronto)Harvard, Pfizer Lecture Hall, 12 Oxford St4:15 pm

Apr 02Prof. Daniel J. Weix (University of Rochester)“No More Nucleophiles: Direct, Selective CrossCoupling of Electrophiles”Boston College, Merkert 1304:00 pmProf. David Crich (Wayne State University) “Stereocontrolled glycosidic bond formation: Achallenge and an inspiration for organicchemists”Tufts, Room P-1064:30 pm

Prof. Richard P. Hsung (University ofWisconsin-Madison)LaMattina Lecture Series“Ynamides: A Modern Functional Group In theNew Millennium”UNH, Room N104 (formerly L103)11:10 am

Apr 03Prof. Irwin Oppenheim (MIT)Boston College, Merkert 130 4:00 pmProf. Thomas Meade (Northwestern University)Harvard, Pfizer Lecture Hall, 12 Oxford St.,Cambridge, 02138 4:15 pm

Apr 04Prof. David Reichman (Columbia University)Harvard, Pfizer Lecture Hall, 12 Oxford St.5:00 pmProf. Erick Carreira (ETH, Zurich)MIT, 6-1204:00 pm

Apr 08Prof. Gong Chen (Penn State University)Brandeis, Gerstenzang 1214:00 pm

Apr 10Prof. Chao-Jun Li (McGill University, Montreal,QC.“Exploration of New Reactivities for SyntheticEfficiency”Northeastern, 129 Hurtig Hall12:00 pm

Apr 11Prof. Phillip Geissler (University of CaliforniaBerkeley)Harvard, Pfizer Lecture Hall, 12 Oxford St.4:15pm Prof. Olof Echt (UNH Physics)Adsorption on Aggregates of Fullerenes: Site-Selective Storage Capacities and AdsorptionEnergiesUNH Room N104 (formerly L103)11:10 amProf. Dr. Andreas Hirsch (Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany)“Chemical Functionalization of SyntheticCarbon Allotropes”Boston College, Merkert 1304:00 pm

Prof. Brandon Ashfeld (University of NotreDame)MIT, 6-120 4:00 pm

Apr 15Prof. Glenn Micalzio (The Scripps ResearchInstitute)Pfizer Research Scientist TBAHarvard, Pfizer Lecture Hall 4:15 pm

Apr 16Prof. Erin Carlson (University of Indiana)Boston College, Merkert 1304:00 pmProf. Scott Phillips (Pennsylvania StateUniversity) “New strategies in reagent design for point-of-use diagnostics”Tufts, Room P-106 4:30 pmProf. Nicolay Tsarevsky (Southern MethodistUniversity)UNH, Room N104 (formerly L103)11:10 am

Apr 17- Apr 18Davison Inorganic Chemistry SeminarProf. Gerard Ferey (Universite de Versaille)MIT, 6-1204:15 pm

Apr 18Prof. Thomas Keyes (Boston University)Boston College, Merkert 1304:00 PMProf. Michael Jennings (Universityof Alabama;Tuscaloosa,AL)“Synthesis of α and β- -C--glycoside NaturalProducts via Oxocarbenium Cations”Northeastern, 129 Hurtig Hall12:00 pmProf. Daniel KirbyUNH Room N104 (formerly L103)11:10 am

Apr 22Dr. Agnes Derecski (Air Products Inc.)Brandeis, Gerstenzang 121 4:00 pm

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Notices for The Nucleus Calendarof Seminars should be sent to:Sheila E Rodman, email:serodman(at)hotmail.com

ACS Northeastern Section at Fenway Park!

Red Sox Game 7:10pm, Friday, May 10th

In the return of a popular NESACS tra-dition, NESACS members, and friendsof NESACS are invited to FenwayPark on Friday, May 10th to watch theRed Sox play the Toronto Blue Jays.Our right field grandstand seats arepriced at $35 and include handlingcharges.

These tickets will go fast! Reserve your seats by mailing yourcheck (payable to NESACS) to AnnaSinger, 12 Corcoran Road, Burlington,MA 01803. Questions (but not reservations) maybe sent to [email protected]. u

mailto:[email protected]

Documents

Nucleus Apr13.pdf