MolPrint3D: Enhanced 3D Printing of Ball-and-Stick Molecular Models

Technology Report Cite This: J. Chem. Educ. XXXX, XXX, XXX-XXX

pubs.acs.org/jchemeduc

MolPrint3D: Enhanced 3D Printing of Ball-and-Stick Molecular Models Paul J. Paukstelis* Center for Biomolecular Structure and Organization, Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States S Supporting Information *

ABSTRACT: The increased availability of noncommercial 3D printers has provided instructors and students improved access to printing technology. However, printing complex ball-and-stick molecular structures faces distinct challenges, including the need for support structures that increase with molecular complexity. MolPrint3D is a software add-on for the Blender 3D modeling package that enhances the printability of ball-and-stick molecular models by allowing the user to selectively split molecules into fragments. MolPrint3D adds pins to the bond and holes in the atom at selected junction points to allow the fragments to be printed independently and assembled. This approach significantly minimizes the number of support structures needed and enables the construction of large macromolecular structures as ball-and-stick models. The MolPrint3D pipeline is described, and several examples demonstrate how improved printability can provide new tools for enhancing student interaction with 3D models. KEYWORDS: Molecular Modeling, Hands-On Learning/Manipulatives, General Public, Demonstrations

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INTRODUCTION Chemistry, in nearly all of its disciplines, is based fundamentally on the spatial arrangement of atoms in three-dimensional (3D) space. For the chemistry student, appreciating these 3D arrangements is a vital step in understanding core concepts, including molecular symmetry in inorganic complexes, stereochemistry and chirality in organic compounds, and the relationship of polymerized monomers in biomacromolecular structures. Interacting directly with physical 3D models has been shown to provide significant educational enhancements.1 However, most chemistry classrooms are still largely dependent on 2D images or graphical representations of 3D structures. 3D printing has begun to find its way into chemistry education for a wide range of topics.2−16 One of the significant barriers to more widespread adoption resides in the ease of printing 3D models on readily available technology at a scale that can reach whole classrooms. Several workflows for creating 3D-printable ball-and-stick molecular models have been described,17−21 but in most instances these are geared toward higher-end commercial printers that are generally found only in designated manufacturing facilities. The reduction in cost and subsequent increased availability of “hobbyist” fused filament fabrication (FFF) 3D printers have led to a significant expansion in the capability of individualsincluding students and instructorsto create and interact with 3D objects. A significant challenge of printing ball-and-stick molecular structures with FFF printers is that layer-based addition requires the use of support structures. The number of supports correlates with the complexity of the molecular structure in 3D © XXXX American Chemical Society and Division of Chemical Education, Inc.

space, leading to increased material consumption and significant postprinting processing that in some cases can make the entire process intractable.2 MolPrint3D is a software tool for splitting ball-and-stick molecular models into smaller fragments to enhance their 3D printability. MolPrint3D is a free, open-source22 add-on for the freely available 3D modeling program Blender.23 Using the standard Blender interface, MolPrint3D allows the user to select junction points between individual bonds (cylinders) and atoms (spheres) to establish independent object groups for 3D printing. The software adds a “pin” to the bond and “hole” in the atom at the junction to allow the objects to be connected after they have been printed. This allows the parts to be positioned and oriented independently on the printer build plate, which can significantly minimize the number of support structures needed to effectively print the entire structure. MolPrint3D also provides automated and interactive tools to help orient models on the printer build plate, support for multicolor ball-and-stick models, strut generation, and tools for manipulating space-filling CPK models for multicolor printing. By enhancing the printability of molecular structures, large numbers of models can be printed in parallel, ultimately allowing wider distribution of physical models to aid in chemistry education. Received: July 22, 2017 Revised: October 25, 2017

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DOI: 10.1021/acs.jchemed.7b00549 J. Chem. Educ. XXXX, XXX, XXX−XXX

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Technology Report

Pinning/Joining

MolPrint3D WORKFLOW The following steps describe the basic workflow of MolPrint3D. Figure 1 provides an overview of these main

Following group selection, pinning creates the pin and hole structures in the defined junctions and simultaneously unionizes the objects in each group to create a fully manifold (“watertight”) mesh object. Cylindrical pins are used by default, but this can be adjusted using the Pin Sides integer parameter. Cylindrical pins allow rotation around the junction point, while triangular or rectangular pins can be used to limit the number of possible assembly orientations. The pin-to-bond size ratio can be set independently for covalent junctions and hydrogenbond junctions when thinner or thicker pins are desired. Flooring and Export

Flooring rotates the final pinned models to find an optimal orientation to sit on the printer build plate (orthogonal to the z axis in the Blender 3D view). In many instances this can be automated for all of the objects in the scene using the Floor All button. Selective Floor allows user interaction to pick one or more faces of the convex hull object in Blender Edit Mode to direct the face normal (or average normal if multiple faces are selected) onto the printer build plate. Finally, models can be exported as stereolithography (*.stl) files that are ready for scaling and printing.

Figure 1. MolPrint3D workflow. An idealized model of adenosine triphosphate is shown at the various steps in the MolPrint3D workflow. The imported VRML model (first panel) is grouped into three separate objects corresponding to the nucleobase, ribose, and triphosphate by selecting the appropriate adjacent atoms and bonds (black arrows, second panel). Each group is automatically uniquely colored. The pinned and joined model is separated to see the pins (red arrows, third panel). Finally, the models are floored (last panel) to provide an optimal orientation for sitting on the printer build plate that minimizes the need for support structures.

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EXAMPLES

Disubstituted Cyclohexanes

steps using an example molecule. Installation instructions and links to example videos are provided in the Supporting Information. Figure S1 shows the MolPrint Toolbar, where the user initiates each of these steps.

As part of a planned lesson introducing chair flipping of dimethylcyclohexanes, atomic models of equatorial and axial conformers of trans-1,2-dimethylcyclohexane were rendered as ball-and-stick models in PyMol and exported as VRML scenes. To demonstrate the different ways these models could be split, the axial conformer was pinned at the methyl carbon substituents, while the equatorial conformer was pinned at the carbon 1 and carbon 2 positions (Figure 2A). The resulting

Import/Cleanup

MolPrint3D uses Virtual Reality Modeling Language (VRML) scene files. These files can be generated by a variety of molecular visualization software packages, including freely available programs such as PyMol,24 UCSF Chimera,25 and Jmol.26 VRML scenes are imported through the MolPrint Toolbar and allow the user to set the number of vertices each primitive object in the scene will have. High primitive divisions enhance the final models’ appearance at the expense of operation speed and final file size (Figure S3). Following import, the scene is “cleaned” to remove any unnecessary objects associated with VRML scenes. Group Selection

MolPrint3D generates an interaction list between atom and bond objects in the cleaning step to allow group selections. Selecting an interacting atom and bond pair denotes a junction. When a junction interrupts interactions between contiguous atom/bond objects, a new group is defined. By default, each group is colored differently in the Blender 3D view screen to provide immediate visual feedback during the grouping process. Automated tools for group selection are geared toward macromolecular structures. Cylinder objects below a userdefined threshold can be recognized as coordination/hydrogen bonds. These bonds and the associated atoms may be selected with the Select H-bonds button. For nucleic acid models, selection of glycosidic (C1′−N1/N9) and phosphate−O3′ linkages are predefined. For proteins, linkages between backbone α-carbons and carbonyls can be automatically selected. These automated selections are dependent on the defined sphere radius for each atom type. Because scaling of van der Waals radii varies slightly among software visualization packages, radii for different atom types can be defined in the Atom/Bond Preferences subtab.

Figure 2. 1,2-Dimethylcyclohexanes. (a) The axial (blue, yellow, violet) and equatorial (green, gray, pink) conformers were split at the substituent groups. The left panel shows the processed models before the floor operation, and the right panel shows the models after flooring. The z axis is orthogonal to the printer build plate. (b) Complete printed models. The left panel shows the six independent objects that were printed, and the right panel shows the final assembled models, which have dimensions of ∼50 mm × 48 mm × 31 mm. The approximate total build time for both models at 60 mm/s and 0.2 mm layer height was 65 min.

models were scaled and printed on a typical FFF printer (Hictop Prusa i3) using polylactide (PLA) filament at 0.2 mm layer height with three exterior shell layers and 50% infill (Figure 2B). These models parallel the use of molecular model kits that have been used extensively in organic chemistry teaching but offer several advantages. First, the students do not need to B

DOI: 10.1021/acs.jchemed.7b00549 J. Chem. Educ. XXXX, XXX, XXX−XXX

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obtain their own model kits, which can be a burden in some cases. Further, they do not need to bring multipiece model kits to the classroom in order to follow along. Finally, the students’ attention can be focused on particular details of the molecular model that coincide with the lesson plan. In this simple example, students can easily manipulate the model to view it as a Newman projection, visualize the dihedral angles at the substituted positions, and determine the number of gauche butane interactions in the different conformers that contribute to the relative stability of the two conformers. Different substituent groups can easily be exchanged if desired, and the cylindrical pins and holes allow rotation around the bonds, enabling the students to find positions of higher or lower steric strain. Importantly, the ability to print many models in a single build run at a reasonable price expands the options for using such models in a classroom setting. The cost of each model is estimated at ∼$0.22 on the basis of consumed filament (assuming a cost of $25.00 per kilogram). This affordability makes it feasible to print several different disubstituted cyclohexanes (e.g., cis- and trans-1,2- and -1,3-dimethylcyclohexane in the axial and equatorial conformations) for each student as physical models that they can interact with and compare during the lecture. When feasible, students could also keep the models to assist as study aids.

Figure 3. DNA duplex. (a) The six unique models processed from an idealized B-DNA 10-mer duplex. Backbone models are printed in gray; the G−C nucleobase pair is printed in green and the A−T nucleobase pair in blue. The assembled DNA duplex of 10 base pairs is shown (b) perpendicular and (c) parallel to the helical axis. The final assembled model dimensions are 26 cm × 15 cm × 15 cm. The approximate total build time per base pair at 60 mm/s print speed and 0.2 mm layer height was 94 min.

Biomacromolecules

Previous examples of 3D printing of biomolecules for educational purposes have been largely restricted to spacefilling and surface representations.7,20 Space-filling models or molecular surfaces can provide important insights into some macromolecular features but can lose other important details available in ball-and-stick models. The utility of MolPrint3D for printing macromolecular structures is illustrated with an idealized B-form DNA of 10 base pairs created in Coot,27 represented in Chimera, and processed through the MolPrint3D pipeline. Though it may be possible to print this model as a single object, the final object size would be limited by the printer build plate size, and the number of support structures needed would make postprocessing extremely arduous if not impossible (Figure S4). The MolPrint3D pipeline was used with automated group selection features to split each base pair of the model into independent nucleobase pairs (connected by hydrogen bonds) by selecting all glycosidic bonds and to split sugar−phosphate backbone segments by selecting all phosphates (Figure S5). Because the starting model is idealized, the processed model contains only six unique segments: the backbones of each nucleotide type are subtly different, leading to four models and the two base pairs. However, these automated tools can be used to split even complex models that contain many unique segments, including the ∼27 kDa structure of yeast tRNAPhe (Figure S6). To recreate a segment of the B-DNA duplex, 20 backbone segments and 10 base pairs (five of each type) were printed on FFF printers (Hictop Prusa i3 and FlashForge Creator Pro) in several PLA colors at 0.2 mm layer height with three external shell layers and 50% infill (Figure 3A). These base pair units were assembled into a B-DNA model (Figure 3B). This model provides a number of features that would not be as readily observable in surface or space-filling representations, including the atoms presented in the major and minor grooves, the pseudodyad symmetry, and nucleobase stacking interactions (Figure 3C).

As part of an existing course focused on nucleic acids, these models, along with equivalent A-form DNA models, were used as part of an examination. For a class of 50 students, 25 A-DNA and 25 B-DNA base pairs were distributed to the students with their exams. Using the models, the students had to answer questions on the exam that asked them to identify the sugar pucker, base pair identity, and backbone conformation. After the exam, the students were encouraged to put their models together into larger duplexes to help understand how local conformation differences lead to different macromolecular conformations. The MolPrint3D pipeline can be used in a similar manner to create models that help students explore amino acids.28

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CONCLUSIONS The MolPrint3D pipeline provides a rapid and intuitive way to simplify molecular ball-and-stick models for 3D printing. Splitting models into smaller segments that can be readily assembled after printing allows for cost reduction by eliminating the need for extensive support structures and improves the ability to print many models in a single printer run. These enhancements will dramatically improve the ability of instructors to print molecular models for whole classrooms and ultimately provide new tools for students to understand important chemistry concepts.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available on the ACS Publications website at DOI: 10.1021/acs.jchemed.7b00549. Installation and usage instructions and Figures S1−S6 (PDF) C

DOI: 10.1021/acs.jchemed.7b00549 J. Chem. Educ. XXXX, XXX, XXX−XXX

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(18) Kaminsky, W.; Snyder, T.; Stone-Sundberg, J.; Moeck, P. Oneclick preparation of 3D print files (*.stl, *.wrl) from *.cif (crystallographic information framework) data using Cif2VRML. Powder Diffr. 2014, 29 (S2), S42−S47. (19) Rossi, S.; Benaglia, M.; Brenna, D.; Porta, R.; Orlandi, M. Three Dimensional (3D) Printing: A Straightforward, User-Friendly Protocol To Convert Virtual Chemical Models to Real-Life Objects. J. Chem. Educ. 2015, 92 (8), 1398−1401. (20) Van Wieren, K.; Tailor, H. N.; Scalfani, V. F.; Merbouh, N. Rapid Access to Multicolor Three-Dimensional Printed Chemistry and Biochemistry Models Using Visualization and Three-Dimensional Printing Software Programs. J. Chem. Educ. 2017, 94, 964. (21) Wood, P. A.; Sarjeant, A. A.; Bruno, I. J.; Macrae, C. F.; Maynard-Casely, H. E.; Towler, M. The next dimension of structural science communication: simple 3D printing directly from a crystal structure. CrystEngComm 2017, 19 (4), 690−698. (22) MolPrint. https://github.com/paukstelis/MolPrint (accessed October 2017). (23) Blender Foundation. https://www.blender.org (accessed October 2017). (24) The PyMOL Molecular Graphics System, version 1.8; Schrödinger, LLC: New York, 2016. (25) Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSF ChimeraA visualization system for exploratory research and analysis. J. Comput. Chem. 2004, 25 (13), 1605−1612. (26) Willighagen, E.; Howard, M. Fast and Scriptable Molecular Graphics in Web Browsers without Java3D. Nat. Precedings 2007, DOI: 10.1038/npre.2007.50.1. (27) Emsley, P.; Lohkamp, B.; Scott, W. G.; Cowtan, K. Features and development of Coot. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 66, 486−501. (28) MolPrint3D was used to create a model kit of all 20 standard amino acids that allows assembly and backbone torsional rotations. See: The 20 Standard Amino Acids. https://www.thingiverse.com/ thing:2175399 (accessed October 2017).

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Paul J. Paukstelis: 0000-0001-8536-4361 Notes

The author declares no competing financial interest.

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ACKNOWLEDGMENTS P.J.P. acknowledges fund ing sup port fro m NSF (DMR1149665). REFERENCES

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DOI: 10.1021/acs.jchemed.7b00549 J. Chem. Educ. XXXX, XXX, XXX−XXX