Gauri Misra E ditor Introduction to Biomolecular Structure and Biophysics Basics of Biophysics Introduction to Biomolecular Structure and Biophysics Gauri Misra Editor Introduction to Biomolecular Structure and Biophysics Basics of Biophysics Editor GauriMisra AmityUniversity Noida,UttarPradesh India ISBN978-981-10-4967-5 ISBN978-981-10-4968-2 (eBook) DOI10.1007/978-981-10-4968-2 LibraryofCongressControlNumber:2017952062 #TheEditor(s)(ifapplicable)andTheAuthor(s)2017 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilarmethodologynowknownorhereafterdeveloped. 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The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Dedicated to The lotus feet of Shri Radha Krishna and Goverdhannathji Foreword by Prof. Joel L. Sussman Receivingisnotalwaysimportant;however,givingbacktosocietycanbeincredi- blysignificant.Thisbook,IntroductiontoBiomolecularStructureandBiophysics: Basics of Biophysics, is an excellent volume of Dr. Gauri Misra to present the fundamentalsandadvancesinthefieldofBiophysicstothescientificcommunity.A journey beginning from the basic macromolecular structure, their functioning, interactions transcending to the methodology that includes the classical and new approachesmakesthiseffortincrediblyworthwhile.Contributionfromtheexperts in the field enhances the quality of the content. Reading about new folds and structures, e.g., the Roadblock and Longin folds, is fascinating and will clearly stimulatethereaderfromneophytethroughexpert. Thebook goes fromclassical biochemistry, e.g.,amino acids,primary through quaternary structures, to very recent discoveries such as intrinsically disordered proteins.Newdiscoveriesandcreativethoughtprocesskeeptheflameofscientific curiosityignited.Themagnitudeofworkdonetobringforththenewadvancements in the field makes the book unique. The principles of the most complex of techniques,e.g.,thelatestdevelopmentsofcryoEMandtheirimpactonstructural biology, are explained in a very clear manner so that the student’s enthusiasm remainsintactwhilereading.Thisbookwillbeusefultopeopleworkingnotonlyin biophysics but also in other scientific disciplines from chemistry through life sciences.Thetextisstrengthenedenormouslybybeautifuldiagrams. Istronglybelievethisbookwillbeareader’sdelightprovidingcomprehensive understandingofmacromolecularstructureandfunctioning.Itwillbeanexcellent introductionforstudentstowardsbiophysicsandwillclearlyhelpthemtodevelopa widerperspectiveofthefield. DepartmentofStructuralBiology JoelL.Sussman WeizmannInstituteofScience Rehovot,Israel vii Foreword by Shekhar C. Mande IampleasedtowritethisforewordonthebookeditedbyDr.GauriMisra.Having browsedthroughthebook,Iamveryhappytonotethatthebookaddressesseveral important aspects of modern Biophysics. Dr. Misra herself is a well-trained biophysicist; therefore she is in a good position to edit such a book. The field of Biophysics has seen several important developments in recent years, such as the advent of cryo-electron microscopy for determining high-resolution structures of proteinsandmacromolecularassemblies,super-resolutionmicroscopyforhigh-end imagingofbiologicalsystems,hydrogendeuteriumexchange,etc.Forthestudents, to keep up with these developments is difficult, unless guided by trained biophysicists in these areas. Dr. Misra has clearly attempted to do so by bringing togetherexpertsindifferentfieldsandwritingchaptersontheseaspects.Moreover, thefundamentalsofbiophysicshavebeenwellcoveredsothatstudentsdonotmiss the basics while trying to understand the modern developments. This book also provides insights into different kinds of biomolecules, including polypeptides, nucleotides, membranes, lipids, etc., in sufficient details. The structural insights intofunctioningofvariousmacromoleculesareexplainedwiththehelpofseveral illustrations.Moreover,manyusefulresourcesareincludedaspartofchapters.This bookcoversareas,suchasproteinfolding,higher-ordernucleicacidstructures,new protein folds, conformational aspects of proteins with functional implications, thermodynamics of protein/DNA stability, etc. Dr. Misra’s creative contribution asanauthoronthechapteronproteinstructureisworthyofappreciation. Thus,a good blend of fundamental biophysics, structural biology, and modern developmentsinbiophysicshasbeenachievedinthisbook.Thisbookhasattempted toprovidebasicunderstandingofsimpleandcomplexexperimentalandtheoretical aspectsofbiophysics.Iamthereforesurethatstudentsofbiophysicsattheunder- graduate,postgraduate,anddoctorallevelswillfindthisbookveryuseful. Director,NationalCentreforCellScience ShekharC.Mande Pune,India ix Preface The present book is the beginning of a new chapter in my academic journey. A successfulaccomplishedresearchcareerignitedwithinmethedesiretodisseminate theknowledgetoyoungstudentswhicharedesirousofbuildingacareerinscience. I joined the university structure and started teaching biophysics and structural biology to the undergraduate, postgraduate, and doctoral students. Interaction withthestudentsintroducedmetotherealitythattheyhaveaninherentapprehen- sion for these subjects as the available resources for most of the underlying conceptsinthesesubjectswereeitherresearcharticlesoracademicreviews.They expressedtheirdesiretohaveareferencebookwhichcouldencompassacompre- hensive collection of basic principles in biophysics and recent research developmentsintheconcernedfield.Thiswasthedrivingforcebehindtheconcep- tionofthisbook. Thelastfewdecadeshaveevidencedtremendousgrowthinthemacromolecular data supported by advances in technology and methodology. This upsurge in the information about proteins, DNA, and lipid structure along with fundamentals of various classical and advanced biophysical techniques used in drug discovery process needs to reach out to students in a language that is elucidating and does drawextensivelyuponacademicjargon.Thisunderlyingmotiveisbeingattempted atinthetreatmentofideas,concepts,andexperiencespresentedinthisbook.There are nine chapters that form the framework of this book. The idea to encompass knowledgespanningfromwhatisknowntowhatisunknowninthewritingsfrom theexpertsinthefieldresultedinaconcertedefforttojustifythevarioustopics.We sincerely hope our efforts will be embraced by students with appreciation and enthusiasmforlearning. Organization of the Book I would like to present an overview of ideas that inform the organization of this book. In doing this, I would also like to foreground the salient and novel features thatmightdrawtheattentionofreadersandmakeitinterestingandengaging.The bookisstructuredinninechaptersthatbringtostudentsinterestingdimensionsof humanunderstandingthatrelatetothesubjectinfocus. xi xii Preface Thefirstchapterhighlightsthefundamentalsofproteinstructureandfunctioning withemphasisontheroleofvariousstructuralfoldsandmotifs.Therecentresearch findingsinvolvinganewfoldhavenowenhancedourknowledgeinthefield.The newerdiscoveryandsomeimplicationsfromthisworkhavebeenincorporated. The second chapter elaborates the basic process of protein folding which is responsible for attributing them with the multitude of functions. An additional information on the computational understanding of this process including the variousintermediatesinvolvedisbeingexplained. ThethirdchapternavigatesthroughthebasicsofDNAandRNAstructurewith underlying structural principles and properties. A brief outline toward the various methodsusedfortheidentificationofthesestructuresispresentedinthelastsection ofthischapter. The fourth chapter extends the basic knowledge of nucleic acid structure to higher-order structures considering the latest developments in this domain that involves the exhaustive details of various higher-order structures, chemical principlesinhigher-orderstructuralorganization,thermodynamicparameters,ther- apeuticusage,andotherbiologicalapplicationsofthesestructures. The fifth chapter discusses the various aspects of macromolecular interactions, bindingenergetics,models,andotherstructuralaspectsoftheseinteractions. Thesixthchapterdealswithlipidsandtheirclassificationandstructuralorgani- zation, variouslipid assemblies, andtechniques used for studying thesestructures withimplicationsinvariouscellularprocessesandhumanhealth. The seventh chapter specifically addresses the biophysical concepts in mem- brane biology. It highlights the different membrane parameters relating to their functioning. The physiological and metabolic relevance of various membrane- associatedtransportprocessesisalsodiscussed. Theeighthchapterexplainsindetailthetechniquesthatarecommonlyusedin biophysics. The principle behind these techniques and the brief outline of instru- mentation,recentadvancesinthefield,andbiologicalapplicationsareelaborated. Theninthchapteraddsanewdimensiontothisbookthatintricatelyprovidesthe knowledge about new biophysical techniques that have been recently gaining popularitytogainnewperspectivesofmacromolecularstructure,functioning,and interactions. Theunderstandingofscienceisincompletewithouttheaidofvisualsthathelpus envision and mentally model the structures and processes involved. In this book, there has been a consistent effort from all the authors to include beautiful and informative illustrations and visuals for explaining the various structures and processes. The text has been kept simple, concise, and easy to understand. An effort is made to use a lucid language without compromising on the content of scientific concepts and the rationalities in order to match the expectations of its prospectivetargetaudience. AmityUniversity,Noida,India GauriMisra Acknowledgments A book is incomplete without the efforts of several people who contribute and supportinvariousrolesandcapacities.Iwouldliketoextendmysincerethanksto all the contributing authors for their persistent efforts to bring the best for the enrichment of the target audience. I extend special thanks to Dr. Juliana Smetana forhertimelyhelpandperiodicfeedback.Theroleofallthestudentswhodirectly or indirectly played a role in shaping this idea to reality is acknowledged. The concernedprojecteditorinSpringerNature,IndiaOffice,Dr.BhavikSawhneyand coordinatorMs.SaanthiShankhararamanhavehelpedinmanywaysbyexpediting theprocessofreviewandkeepingmeabreastwiththeofficialdevelopments. While efforts of some are explicit and visible, some of them have consistently supportedmeandmywork.Itakethisopportunitytoextendmyheartfeltthanksto my mother Mrs. Kamla Misra, my spiritual teacher the late Bhaktivedanta Shri NarayanSwamiMaharaj,mygrandmotherthelateMrs.ShantideviMisra,andmy grandfather the late Mr. Anand Swaroop Misra for their persistent motivation in supportingmecarvemycareernicheandallthechallengingendeavorsthatIhave takenupsuchaswritingthisbook.Theloveandsupportofallteachers,friends,and colleagueshavetranslatedthisworktoasatisfactoryconclusion.Ihopethefuture bestowsmorepossibilitiesforconstructivefeedbackgivingthenecessaryimpetus to much more academically empowering efforts for the benefit of younger generations. xiii