Molecular Logic (MoLo)molo.concord.org/research/molo_activities.pdf · The goal of the Molecular Logic (MoLo) ... Solids, Liquids and Gases ... Students determine that diffusion results

The Molecular Logic Final Report 1

Molecular Logic (MoLo)

ACTIVITIESOverview of ActivitiesCurriculum

Initial Development – Year OneDevelopment and Formative Assessment of the Molecular Logic Materials- YearTwo

The Stepping Stone ActivitiesActivity ComponentsAdditional Models and Model-based Components

Database of ActivitiesThe Blackboard Tutorial and Other Assistance for TeachersTechnical SupportMolecular Workbench Software

Developments in the Simulation EnginesDNA to Proteins3DNew Features, New Apparatus and New GUIs

The Authoring Interface and Scripting EnginesDevelopments of the Assessment SystemImprovements on Networking CapabilityImprovements in PerformanceMiscellaneous Improvements and Special Activities

For coherence, Assessment and Evaluation activities will be included in Findings.

OverviewThe goal of the Molecular Logic (MoLo) project has been to improve the ability ofstudents to understand fundamental biological phenomena in terms of the interactions ofatoms and molecules. The Molecular Logic project enhances biology courses with guidedexplorations of powerful atomic and molecular computational models. These models areembedded in an easily used on-line database of over 180 activities. The database wasdeveloped to provide teachers and students with access to models and model-basedactivities that meet their needs, and is searchable by keyword, concept, NSES Standard orAAAS benchmark, or by chapter of commonly used biology textbooks.

There are some specific molecular properties and behaviors, many of which typically fallin the province of physics and chemistry, that constitute a foundation of many biologicalphenomena, These properties and behaviors include such basic concepts as polarity,diffusion and osmosis, weak attractions, polymer folding, and template-based synthesis.Selected and placed in sequence, they make up a ”Molecular Logic” underpinningbiological phenomena.


To support these concepts we developed activities with interactive, dynamiccomputational models, each focused on a molecular concept underpinning a traditionalbut “hard-to-teach” topic in biology such as the role of semi-permeable membranes intransfer of materials in and out of living cells, protein folding and proteins self-assembly,or DNA replication.

Our model-based activities are based on our signature software, the MolecularWorkbench, a dynamic molecular modeling environment that computes the behavior ofatoms and molecules from first principles. These models inhabit a territory between pre-set animations with limited interactivity, and powerful professional dynamic modelsdeveloped for use in research, usually lacking a user-friendly interface. MoLo activitiescombine real science-grade simulations, on the one hand, with the simplicity andinteractivity that make for good education.

The activities can be used in a range of settings, from classroom demonstration tointeractive exploration and experimentation by individuals or teams of students. Wefocused particularly on building in extensive interactivity. With deep interactivity,students can devise experiments with atoms and molecules, vary parameters and compareconditions.

Curriculum

Initial Development – Year One

Initial Curriculum Review.We proposed a modular structure of activities, in ascending order of molecularcomplexity, from atoms to a system of atoms to large biological molecules. To obtain aninitial outline of this process, we used a Modified Backwards Design (Shumway, S., &Berrett, J., 2004), setting initial goals and objectives, checking them against an inventoryof existing and feasible Molecular Workbench models, and also against sets of centralphysics and chemistry concepts, key biology texts, and biology standards.

In addition, an early initial workshop for Cambridge Biology teachers using ourpreliminary activities was given in order to obtain their suggestions for most neededmodels and their related objectives. Teachers gave us specific suggestions for areas inwhich new models were needed. Teachers and project advisors were also asked abouttheir modeling needs in several districts locally.

Activity Redefinition.The initial list of activities was made available to the first Advisory Board conference,together with the draft database. Feedback from advisors was used to inform the learningobjectives, and to focus our efforts on a core set of Physical-Chemical “Stepping Stones,”basic activities that would serve to introduce a larger suite of activities.


Development and Formative Assessment of the Molecular LogicMaterials - Year Two

Following the advice of our board in its first annual meeting, we selected among manyactivities a subset to serve as "Stepping Stones,” entry activities upon which to focus ourattention. These would serve as doorways to larger molecular content areas in Biology.Each activity emphasized one of the basic physical-chemical-biochemical principlesunderlying biological processes (see list below). These were presented for review byboard members and scientists, and received enthusiastic feedback. Over the life of theproject they were developed, tested in the classroom, revised, using feedback from thetesting, and retested (see Findings).

Sequential Logic. Stepping Stones were designed to be not only entries into large conceptareas, but also to build upon each other, from atoms to simple molecules, and fromsimple molecules to DNA and Proteins. One thread running through the Stepping Stonesequence is the idea of random motion at the atomic scale. The first Stepping-Stoneexplores the idea that atoms and molecules are constantly moving, which is calledBrownian motion. In this activity, students add particles to a model and observe theirinteractions with other particles. They learn that their random motion is a result of manycollisions from all sides.

Using the modeling tool, students experiment by increasing the temperature of the systemto determine how heat affects molecular motion. Stepping Stone two elaborates on theconcept of random motion to explain diffusion and osmosis. Throughout the followingactivities, then, students can control the amount of heat in the system, and infer, predictand observe how it will affect the process.

Another thread running through the sequence is charge (Coulomb force) and polarity. InStepping Stone three, students learn about electronegativity, and how it results indifferent types of bonds: non-polar covalent, polar covalent, and ionic. Students areasked to reason about the polarity of water. In Stepping Stone four, they view a varietyof 3D models of biomolecules, and see that many have polarized surfaces. In the fifthStepping Stone, they explore the variety of weak attractions between molecules,including polar and non-polar attractions, and hydrogen bonds. In Stepping Stone sixthey can experiment with the role of these weak attractions in a two-dimensional modelof protein folding. Here they also experiment with molecular recognition and self-assembly of individual molecules into larger molecular assemblies (quartenarystructures), employing the interaction of weak, intermolecular attractions with thedisruptive power of thermal motion seen in earlier Stepping Stones.

Thus, from simple concepts of random motion and stickiness between particles, a more


sophisticated view of the molecular world emerges. Armed with this understanding,students can take on an exploration of protein structure and function using 3D models(Stepping Stone 7), and experiment with chemical reaction models in the context ofcatalysis and enzymes (Stepping Stone 8).

The Stepping Stone sequence culminates with an exploration of the central dogma ofmolecular biology. In Stepping Stone 9, students work with a model that shows theentire process from genes transcription and translation, through protein folding of thenewly synthesized protein. Students can edit the DNA nucleotide sequence of the geneand observe how it will affect the sequence of amino acids in the protein and the shape ofthe resulting protein. With this notion, they can generate different mutations. Forexample, by inserting or deleting a nucleotide, they create a frame shifting mutation, andcompare the effect with less dramatic substitution mutations. Finally, in Stepping Stone10, students make a transition from molecular to cellular models of heredity to explorethe connection between genotype and phenotype.

The Stepping Stone Activities0.1 Prerequisite - Atomic Structurehttp://MoLo.concord.org/database/activities/47.html

Students construct models of atoms with properties of particular mass, charge andstability by adding or subtracting neutrons, protons and electrons to a model atom.

0.2 Prerequisite - Solids, Liquids and Gaseshttp://molo.concord.org/database/activities/180.html


Students view the motion of molecules in solid, liquid, and gas states, and thendiscuss how this model helps describe the macroscopic properties of each state.

1. Brownian Motion: Atoms and Molecules Are Always Movinghttp://molo.concord.org/database/activities/40.html

Students see that when a small particle is surrounded by water molecules (or otheratoms/molecules), the resulting motion looks random; the particle appears not tomove in straight lines. They trace the path of individual particles and discover thatthis apparently random movement is due to many atoms or molecules moving instraight lines until they collide with other atoms or molecules, and that thismovement can be affected by temperature.

2.0 Spatial Equilibrium: Modeling a Gas.http://molo.concord.org/database/activities/220.html


Students observe a model of a gas, and are challenged to prevent spatialequilibrium while the model is running, and learn how spatial equilibrium isdetermined; they demonstrate that all initial states result in a similar equilibriumdistribution of spatial locations of atoms. They describe that a gas in spatialequilibrium is a point where the average number of particles is the same in anyregion.

2.1 Diffusion and Osmosishttp://molo.concord.org/database/activities/223.html

Students determine that diffusion results from random motion and /or collisions ofparticles, learn that particles diffuse from high concentration to low concentration,and explore simple diffusion across a semi-permeable membrane.

3. Strong Chemical Bondshttp://molo.concord.org/database/activities/235.html

Students change electronegativities of atoms to create different types of strongbonds. They explain the relationship between types of bonds and the electro-negativities of the bonded atoms as well as the reasons polar bonds form and their


relationship to electron clouds as they are attracted to two different nuclei.

4. The Tree of Life's Macromoleculeshttp://molo.concord.org/database/activities/226.html

Students identify typical molecular building blocks (monomers) that formbiological macromolecules, determine the types of atoms that make up mostbiopolymers, and reason about the uniformity of the atomic level of life'smolecular building blocks

5.0 Weak Attractions Between Moleculeshttp://molo.concord.org/database/activities/227.html

Students learn about weak attractive forces between molecules, compare them tostrong bonds, explore the strengths of the weak forces and determine theimportance of surface area as it relates to the weak forces. They look specificallyat hydrogen bonds and the importance of charge as it relates to the weak forces.Finally they are challenged to design their own models of molecules that areattracted to each other.

5.1 Dissolvinghttp://molo.concord.org/database/activities/186.html


Students discover that the process of dissolving is the result of interactionsbetween water molecules, between particles of the substance being dissolved, andthe interactions among those particles and water. Students reason that, fordissolving to occur, the interactions between molecules of the substances withwater molecules must be stronger than their attractions to each other.

6.0 Protein Foldinghttp://molo.concord.org/database/activities/225.html

Students discover how the properties of amino acids (charge and polarity) affectthe shape of a peptide chain. They explore the complex interactions of aminoacids with each other and with the surrounding water molecules or lipids. SickleCell Anemia is used as an example of disease caused by a single amino acidsubstitution.

6.1. Self-Assemblyhttp://MoLo.concord.org/database/activities/231.html


Students learn the necessary conditions for self-assembly (random motion andmolecular stickiness), experiment with some sample models of self-assemblingbiological structures, (dimers, fibers and microtubules), and then design their ownself-assembling structures.

7. Insulinhttp:/molo.concord.org/database/activities/236.html

Students explore both 2D and 3D models of proteins in order to discern the fourlevels of structure of a small protein, the hormone insulin. They connect thestructure to its triggering function at a receptor.

8. Reaction Rates, Catalysis, and Pasteurizationhttp://molo.concord.org/database/activities/230.html

Students manipulate a model, including graphs, of bond energy/dissociationenergy; they describe the relationship of temperature and reaction rate andmanipulate the activation energy of diatomic pairs.

9.0. DNA to Protein Synthesishttp://molo.concord.org/database/activities/240.html


Students explore the way the sequence of DNA dictates the shape of a protein,and they can substitute, delete or replace nucleotides in a strand of DNA. Theythen engage the revised DNA in replication and transcription. Students alter theamino acid sequence in a protein chain and observe how the change affectsfolding and conformation of the model protein.

9.1 Mutations: Changing the Genetic Code:http://molo.concord.org/database/activities/102.html

Students experiment with types of point mutations and the location in which thesemutations occur and explore the impact on the shape of a protein.

10. Genotype to Phenotype - Introduction to Biologicahttp://molo.concord.org/database/activities/152.html


This activity introduces students to models of chromosomes, genes, and alleles,and stresses the connection between genotype and phenotype. It was extractedfrom the larger Biologica software developed by another team at ConcordConsortium. Students edit a genotype of a dragon and observe resultingphenotypes.

Activity ComponentsEach activity was self-contained, and designed to be completed within one class session.Each had its own educational goals, student instructions, one or more models, andassessments, designed for one or two class days (see Appendix A: Sample Activity).Activities did not include homework per se, but extensions and connections that could beused for homework. Database pages provided, in addition:

Teacher and student viewsOverview and Learning ObjectivesAssessmentClassroom PracticeCentral Concepts, plus concept and activity mapsTextbook ReferencesExtensions and ConnectionsTechnical and pedagogical prerequisites,Links to NSES Standards and AAA BenchmarksCode for level of scaffolding availableCode for ‘editability”Alerts for technological changes

Our intent was to have one activity per Stepping Stone, but the complexity of some ofthese steps resulted in several being divided. The final number of Stepping Stones testedwas 14, with two prerequisites. A full implementation would, therefore, require about 14-20 hrs of class meetings.In order to facilitate adoption of activities for summative testing in the last year, a shortersequence of four activities was developed. This strategy will be more fully described inthe Findings.

Each activity ended with the submission of student answers, or, in activities authoredexclusively in Molecular Workbench, a full student report, with snapshots of modelstates, sometimes annotated. These reports are automatically generated within MolecularWorkbench and uploaded by students to a database viewable by teachers. They can also


be printed or saved as HTML on a local computer.

Additional Models and Model-Based Activities

Additional activities, beyond the Stepping Stones, were developed with several levels ofscaffolding: Fully-developed (with multiple pages of student steps, including assessmentquestions and reporting capability), Interactive (some model manipulation) andPresentation/Demo. This layering permits activities to evolve to their best pedagogicalform. These additional activities were made available, as were the Stepping Stones, in thedatabase for ease of search, and in the libraries of the stand-alone Molecular Workbench.

Database of Activities

Figure 2: Choices for locating an activity in the MoLo Database .

All activities were made available in an online MoLo database, designed to provideteachers and students with easy access to models and model-based activities. Users cansearch by keyword, concept, NSES Standard or AAAS benchmark, or by chapter of oneof a set of biology textbooks (see http://molo.concord.org/database ). Extensiveadditional activities are found within Molecular Workbench Libraries. Activities caneither be launched directly within the browser at the database site using Java Webstart, orrun within Molecular Workbench ‘s “Activities” section.(http://mw.concord.org/modeler/ )(see Appendix B: Database).


Database Activity Page

Figure 3: A portion of a database page serving an activity.

The database was reviewed favorably on the NetWatch page of Science magazine (Julyvol. 309, 15 July, 2005) (see Appendix C: Netwatch).

The Blackboard Tutorial and Other Assistance for TeachersA Molecular Logic (MoLo) tutorial introducing the component parts of the project withits software and activities was developed for use with Spring 2005 teachers, and wasrevised for Fall 2005 (http://blackboard,concord.org). Key components were based onearlier workshops. The tutorial was developed in Blackboard, a collaborative coursewarefor online courses and tutorials. It contained basic introductory material as well as waysto work more with the software to adapt and author activities (see Appendix D: Tutorial).

Figure 4: A page in the Assignments section of the online MoLo tutorial.

Additional teacher support was made available in the database, as mentioned above, andwithin the Molecular Workbench Software—via a User’s Guide and assistance in


adapting and authoring. Worksheets (see Appendix E: Adapting a Model) were also madeavailable in workshops.

Technical SupportTechnical Assistance staff was on-line and available for assistance. FAQs were writtenand attached to the database. See <http://molo.concord.org/faq/ >. These materialscovered questions about the Molecular Workbench software, getting through schoolfirewalls, loading Java Web Start, and other general questions. The requests for helpfrom staff sharply diminished over the last two years with an uptick at the project’s endcaused by problems with Java. These problems should disappear with the next release ofJava.

Molecular Workbench Software

The Molecular Workbench (MW) software is a science-based learning environment builtaround a set of molecular dynamics engines. Molecular dynamics simulations in MWdemonstrate the atomic-scale mechanisms of fundamental phenomena in physics,biology, and chemistry (Berenfeld & Tinker, 2001; Tinker, 2001b, 2001d). Simulations inMW are based on calculating the motion of atoms, molecules, and other objects in realtime under inter-atomic forces. The forces used are derived from the Lennard-Jonespotentials, electrostatic potentials, bond-stretching potentials, angle-bending potentials,and external fields.

Because it is based on good approximations of physical laws, MW can produce emergentphenomena such as phase changes, crystallization, latent heat, diffusion, solubility,osmosis, absorption, chemical equilibrium, catalysis, self-assembly, and biomoleculeconformation. Some effective forces have been also invented in MW to model difficultsystems. For example, an effective field is used to approximately model the hydrophobicand hydrophilic effects to simulate protein folding. Chemical bonds that have user-controlled energies can be made and broken to simulate chemical reactions (Xie &Tinker, 2006). Large molecules can be created and charges added to them to resemblebiological molecules (Berenfeld, Pallant, Tinker, Tinker, & Xie, 2004).


Students can visualize abstract atomic-scale phenomena, observe emergent behavior,design model-based experiments, and reason about the relationship of atomic-scaleinteractions to macroscopic phenomena in a structured environment. A wide range oftools is available for analyzing the model, including graphs, display options, virtualtemperature and pressure probes, and more.

Figure 5: Users can customize the toolbar of the model with objects and actions.

The software also includes the easy-to-use Molecular Workbench authoring environmentthat supports the design of interactive activities linking atomic-level models to a broadrange of core science concepts. In addition to setting the parameters of the model, theauthoring environment allows the activity designer to provide instructions, scaffolding,and performance assessment instruments related to the model, including open-endedquestions and multiple-choice tests.

Although this software was started in earlier projects, it made significant leaps forward inMolecular Logic.

Developments in the Simulation EnginesThe following lists the additional software capacity developed with the MoLo finding.DNA to Proteins(a) Addition of twenty elements to represent the amino acids.(b) Addition of five elements to represent the nucleotides (A, C, G, T, U).(c) Design of the force fields for hydrogen bonds between base pairs to simulate DNAhybridization.(d) Improvement of the heat bath and heating algorithms so that heat can be added orremoved evenly from all atoms. This removed the artifacts that hotter atoms becomehotter and colder atoms become colder in the original heating algorithm.


(e) Combining the DNA/RNA combo scroller with the molecular dynamics engine tosimulate protein synthesis. This involved devising an algorithm that emulates the growthof a polypeptide from a point where the ribosome is supposed to be located.

Figure 6: A DNA Scroller allows students to code for amino acids.

3D

(a) Incorporation of Jmol for 3D rendering of molecules.(b) Building of first version of 3D molecular dynamics engine. This version allows theuser to set up common crystal structures and perform molecular dynamics simulations forthem.


Figure 7: Students explore Hemoglobin from the Protein Database displayed within theMolecular Workbench using jmol.

New Features, New Apparati and New GUIs

(a) Pre-caching everything automatically(b) Annotations in models: Images, text boxes, and lines(c) Annotations in snapshots (see Appendix F: Pedagogy of Molecular Workbench)(d) MW integrated with a search engine: this allows the user to search within MW(e) Internationalization: Chinese and Russian language support(f) Force-line visualization of electric field(g) Virtual pressure probes

Developments in the Authoring Interface:

(a) Molecular editor: Selecting and moving mode merged; keyboard shortcuts added.(b) Intra-page communication between embedded components through scripts(c) Implemention of undo/redo functionalities for the Molecular Editors.(d) Addition of numeric boxes to display results in numeric forms (e.g. counters).(e) Embedded tables were made editable.(f) Different running averages were added to graphs.(g) Two types of virtual instruments, the virtual X-ray diffraction device and the photonemission and absorption spectrometers, were added.(g) New buttons for filling the selected area with atoms were added.(h) New buttons for creating DNA strands were added.(j) Maxwell speed/velocity distributions were redone.(k) Pair correlation functions became available on the authoring interface.(l) Mean-square displacements analysis became available on the authoring interface.(m) The functionality of importing a set of models from a pull-down menu was added.(l) Universal support for scripts has been built. Scripts can now be set to work fromalmost all kinds of controllers.


(n) HTML text boxes were greatly enhanced. Hyperlinks can now execute scripts uponclicked. Embedded components within HTML text boxes can now be used to controlmodels through the Script Protocol.(o) Script consoles are added as standard controllers for models. Authors who areinclined to using a command-line environment will find these consoles handy whendesigning a model.

ScriptsA scripting environment is under development, which allows the user to do things thatwould be too complex to do from the user interface. MW scripts refer to macros that canbe used to interact with models. All components in MW pages now support MW or Jmolscripts.

The MW scripts now include these features:

(a) Logical expressions in object selection(b) Mathematical expressions(c) Loops(d) System variables(e) User-defined variables(f) Random numbers(g) Most mathematical functions including special functions(h) Use delays in real time to create animation(i) Use delays in model time to automatically change a model while it is running(j) Macros to set and get the properties of objects

Developments of the assessment system:

(a) A wizard allowing students to create multi-page reports on multi-page activities andsubmit these reports to our database was created.(b) A user interface for searching reports and models in the databases was created tofacilitate teachers and researchers to access students' work.(c) The user can now print or save a report in HTML.

Improvements of networking capability:

(a) The Molecular Workbench stand-alone application became self-updatable, in additionto using Java Web Start. If the user runs the Molecular Workbench standalone (i.e.double-clicks on the Workbench.jar file), it will update itself if there is a newer versionavailable. Thus, we can keep those users up-to-date who cannot use Java Web Start tolaunch the software and must therefore run Molecular Workbench as a stand-aloneapplication.


(b) An automatic JNLP generator was added.(c) Databases for models and activities, reports, and comments were constructed andlinked to the Molecular Workbench software through servlets (Java programs running onthe server side). As a result, the user can directly upload to the database and viewuploaded files using the Molecular Workbench user interface.(d) Functionalities that permit the users to upload a single page or a multipage activity tothe database were built.(e) A page and the whole folder can be compressed directly using the MolecularWorkbench. These improvements make the Molecular Workbench software more user-friendly and easier to use.(f) Timeouts (connection opening timeout and read timeout) can now be set.

Improvements in performance:(a) The problem of memory leak is significantly reduced, but not completely solved yet.Memory leak in Molecular Workbench is caused by two sources. The first type is the leakdue to the multiple document interface (MDI), which means when a new window isclosed, the resources it uses are still held in the Java virtual machine, but not returned tothe operating system. This is nearly fixed. The second type is the leak due to thecomponents on the page, which means that some components on the page are retainedeven after the user has left the page. This is likewise nearly corrected. But there is stillsome mysterious interlocking, probably caused by Java itself, which prevents completerecycling of memory under rare circumstances.(b) The Gay-Berne engine was optimized and now runs 50% faster.(c) Some work has been done to make MW run better on Mac OS X. Meanwhile, there isa significant performance improvement of Java on the Tiger version of Mac OS X.

Miscellaneous Improvements

There are many other small improvements in the Molecular Workbench software.

(a) More keyboard shortcuts that are identical to conventional shortcuts were added.(b) The user is given a chance to save all the images stored in the Snapshot Gallery to apage before closing the software.(c) The snapshot function has been improved to allow the user to add a description of theimage, or make annotations using an annotation tool. These will be automaticallyincluded when the report is generated. (see Appendix C: Pedagogy of A MolecularWorkbench Page)(d) Visited textual links are remembered.(e) Last viewing position in a page is saved. As a result, if the user goes back to a visitedpage by hitting the Back button, the page will automatically scroll down to the lastviewing position if the length of the page invokes a scroll bar.(f) Self-running random scripts are generated and set to Jmol when it enters the fullscreen mode. (This mimics a screen saver.)(g) Special activity: Zoom-It: Up and down the scale, loosely based on the Powers ofTen.

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Molecular Logic (MoLo)molo.concord.org/research/molo_activities.pdf · The goal of the Molecular Logic (MoLo) ... Solids, Liquids and Gases ... Students determine that diffusion results