Ten Simple Rules for Creating Biomolecular Graphics
A Visual Guide to the Molecular World
Introduction: The Art of Seeing the Invisible
Imagine trying to understand the complex machinery of a city by only reading written descriptions, without ever seeing a map, blueprint, or photograph. This is the challenge scientists faced for decades when studying the molecular machinery of life.
Biomolecular graphics have revolutionized our understanding of biology by transforming abstract chemical concepts into visually intuitive models that reveal how form connects to function. From the elegant double helix of DNA to the intricate folding of proteins, these visualizations make the invisible world of molecules tangible.
The cliché about a picture being worth a thousand words is particularly poignant in structural biology. The information 'content' of an effectively constructed piece of molecular graphics can be immense, compressing complex spatial relationships and interactions into a single, comprehensible image 1 . As the molecular basis of human disease becomes increasingly clear, the ability to visualize these biological building blocks has never been more critical to scientific communication and discovery.
Nevertheless, creating effective molecular graphics is not easy—neither conceptually, nor in terms of the effort required 7 . Whether you're a researcher preparing a publication, an educator designing course materials, or a student embarking on your first visualization project, these guidelines will help you create clearer, more informative, and more compelling biomolecular graphics.
Key Insight
Biomolecular graphics transform abstract chemical concepts into visually intuitive models that reveal how molecular form connects to biological function.
Impact
Effective visualization is critical for understanding the molecular basis of human disease and advancing therapeutic development.
The Visualization Toolkit: Concepts and Techniques
Before creating effective graphics, it's essential to understand the fundamental representation models and techniques available. Biological molecules exhibit high complexity and diversity, and different visualization methods highlight distinct aspects of their structure and function.
Skeletal Models
Describe backbone structure using lines, sticks, and ball-and-stick representations. Ideal for viewing connectivity and atomic positions.
Cartoon Models
Highlight protein folding and secondary structures with ribbons and schematic representations. Perfect for visualizing overall topology.
Surface Models
Illustrate molecular boundaries and interactions. Show where molecules contact their environment and other molecules.
Key Biomolecular Representation Models
| Model Type | Best For | Visual Elements | Limitations |
|---|---|---|---|
| Lines/Stick | Viewing backbone structure and connectivity | Lines, sticks | Doesn't show volume or space filling |
| Ball-and-Stick | Understanding atomic positions and bond angles | Spheres (atoms), cylinders (bonds) | Can obscure internal structure |
| Space-Filling | Seeing actual volume and spatial occupancy | Spheres with radii proportional to atomic size | Can hide structural details |
| Cartoon/Ribbon | Visualizing protein folding and secondary structure | Ribbons, tubes, arrows | Loss of atomic detail |
| Surface Models | Understanding molecular interactions and binding | Continuous surfaces | Computationally intensive |
Emerging Visualization Technologies
Immersive Visualization
Using head-mounted displays to virtually "step inside" molecular structures 3 .
Level of Detail (LOD) Techniques
Automatically adjusting rendering quality based on viewer focus for real-time interaction 3 .
Artistic Representation Methods
Borrowing from design and illustration to create more visually appealing graphics 3 .
A Detailed Case Study: Visualizing the Molecular Basis of Disease
To understand how these visualization principles apply in cutting-edge research, let's examine a specific case study: the use of cryo-electron microscopy (cryo-EM) to visualize ion channels involved in polycystic kidney disease at Northwestern University's Feinberg School of Medicine 5 .
Methodology: Step-by-Step Visualization Process
The process began with the establishment of the Feinberg Advanced Cryo Electron-Microscopy and Tomography (FACET) core facility, which provided researchers with access to a Glacios-2 Cryo-Transmission Electron Microscope.
Key Equipment in Cryo-EM Visualization
| Equipment/Software | Function | Role in Visualization |
|---|---|---|
| Glacios-2 Cryo-TEM | Electron microscopy | Captures 2D projection images of frozen samples |
| Falcon 4i Detector | Direct electron detection | Records high-resolution images with minimal noise |
| Selectris Energy Filter | Improves image contrast | Removes inelastically scattered electrons |
| Grid Preparation Tools | Sample preparation | Creates suitable substrates for freezing samples |
| 3D Reconstruction Software | Data processing | Converts 2D images into 3D density maps |
| Molecular Graphics Software | Model visualization | Displays atomic models with various representations |
Results and Analysis: From Structure to Insight
The cryo-EM analysis revealed novel molecular mechanisms by which genetic mutations in the PKD2 gene cause polycystic kidney disease. Researchers were able to visualize the ion channel's structure at near-atomic resolution, identifying how specific mutations disrupt the normal function of the protein 5 .
The structural visualization showed precisely how disease-causing mutations altered the chemical features of the channel, explaining why these genetic changes lead to the formation of cysts in the kidney that can progress to fatal kidney failure. This detailed structural information provides a template for developing prototypic drugs to treat polycystic kidney disease by targeting the specific defects caused by different mutations 5 .
Perhaps most importantly, the resulting visualization didn't just represent a static structure—it told a story about dysfunction and pointed toward therapeutic solutions. As Dr. Paul DeCaen explained, "The microscope will allow us to visualize the molecular chemical features of the channel at the atomic level. The resulting structural template will be used to develop prototypic drugs to treat polycystic kidney disease" 5 .
Expert Insight
"While the Human Genome Project helped to enumerate genetic components, this new technology defines their structural protein products and their location within cells to elucidate how we approach therapeutics."
The Scientist's Visualization Toolkit: Essential Resources
Creating effective biomolecular graphics requires both conceptual understanding and practical tools. Beyond the specialized equipment used in cutting-edge structural biology, several resources are essential for everyday visualization work.
Molecular Visualization Software
Packages like PyMOL provide the foundation for creating most molecular graphics, offering a range of representation styles and rendering options 7 .
Biomolecule Characterization Tools
Solutions like the Bio Tool Kit provide specialized functions for mass analysis, sequence analysis, and modification mapping 4 .
Modification Catalogs
Comprehensive databases containing information on over 1,300 biological and chemical modifications for accurate representation 4 .
Rendering and Illustration Software
Specialized tools like Illustrate implement advanced rendering techniques optimized for biomolecular illustration 6 .
Biomolecular Visualization Software Tools
| Software/Platform | Primary Function | Key Features |
|---|---|---|
| PyMOL | Molecular visualization | Publication-quality images, scripting support |
| Bio Tool Kit | Biomolecule characterization | Mass analysis, sequence analysis, modification mapping |
| Illustrate | Biomolecular illustration | Non-photorealistic rendering, ambient occlusion |
| QuickSES | Surface calculation | Fast solvent-excluded surface computation |
| Cytoscape | Biological networks | Network layouts, data integration |
Ten Simple Rules for Effective Biomolecular Graphics
Creating effective biomolecular illustrations requires both scientific accuracy and visual design skill. These ten simple rules synthesize time-tested principles that will improve the clarity and impact of your molecular graphics.
1 Study and Emulate the Masters
Learn from the molecular artistry of legends like Geis and Goodsell, who set the standard for clear and beautiful molecular illustrations 7 . Don't limit yourself to scientific sources—explore principles from statistical graphical design and information visualization advanced by thinkers like Edward Tufte.
2 Articulate Your Purpose First
Before creating a graphic, specifically articulate its purpose. What scientific story are you trying to tell? Who is your audience? The answers will drive every decision about what to include, emphasize, and exclude from your visualization 7 9 .
3 Prioritize Clarity and Consistency
Understanding an illustration shouldn't require detective work. Define clear symbolic and diagrammatic conventions early and adhere to them throughout all figures in a publication 7 . A manuscript with several 3D images will be more understandable if a canonical orientation is established and maintained.
4 Match Representation to Message
Choose visualization styles that align with your communication goals. Use cartoon representations to illustrate protein folding, surface models to show molecular interactions, and ball-and-stick models for detailed atomic views 3 9 . Consider alternative layouts like adjacency matrices for dense network data.
5 Invest Time in Planning and Execution
First-rate molecular graphics are cornerstones of high-quality publications and require considerable patience. As a rule of thumb, spend at least as much time per figure as you would writing two pages of text (approximately 500 words per page) 7 .
6 Implement Strategic Use of Color
Use color purposefully to highlight important features, represent properties, or distinguish between elements 9 . Choose color schemes that are accessible to viewers with color vision deficiencies and that maintain clarity when printed in grayscale.
7 Leverage Captions Effectively
A well-designed figure deserves a well-written caption that explains what is being shown and highlights key takeaways 7 . The caption should make the figure comprehensible even to readers who only skim the visuals.
8 Seek and Incorporate Feedback
Have colleagues critique your works in progress to identify unclear elements or missing context 7 . Fresh perspectives often catch ambiguities that become invisible to creators too close to their work.
9 Balance Realism and Abstraction
While photorealistic rendering can be impressive, simplified or abstracted representations often communicate more effectively 3 . Remove visual clutter that doesn't serve your communicative purpose.
10 Stay Current with Technological Advances
The field of biomolecular visualization continues to evolve with new rendering techniques, hardware acceleration, and emerging technologies like augmented reality that offer new ways to explore and present molecular structures 3 .
Rule Summary for Different Contexts
| Rule | Publication Figure | Oral Presentation | Educational Material |
|---|---|---|---|
| Clarity and Consistency | Critical for detailed study | Simplified for quick comprehension | Balanced detail with clarity |
| Strategic Color Use | Must work in print and digital | High contrast for visibility | Educational color coding |
| Caption/Label Quality | Detailed explanation | Minimal, speaker explains | Educational, self-contained |
| Level of Detail | High, with multiple panels | Low, single focused message | Graded by student level |
| Feedback Incorporation | Essential before submission | Test for audience comprehension | Pedagogical effectiveness |
The Future of Biomolecular Visualization
As we look ahead, several emerging technologies promise to further transform how we visualize and understand biological molecules.
Artificial Intelligence
Foundation models learning the rules of biomolecular structure and function . These AI systems can predict protein folding, generate novel molecular designs, and even suggest visualization strategies.
Immersive Technologies
Virtual and augmented reality creating new opportunities for researchers to interact with molecular models in three-dimensional spaces 3 , manipulating structures with natural gestures.
Multi-scale Visualization
Techniques that allow researchers to seamlessly zoom from atomic details to cellular context 3 , handling increasingly large datasets with efficient algorithms.
These advances come with challenges, including the need for more efficient algorithms to handle increasingly large datasets and the importance of developing standardized approaches that ensure visualizations accurately represent underlying structural data rather than artistic interpretation.
As these technologies mature, they will further blur the line between visualization as a tool for exploration and as a medium for communication, making the molecular basis of life increasingly accessible to researchers, students, and the public alike.
Future Challenges
- Efficient algorithms for large datasets
- Standardized visualization approaches
- Balancing accuracy with artistic interpretation
- Integration of multiple data sources
Conclusion: Visualizing a Clearer Future
Biomolecular graphics have evolved from simple physical models to sophisticated digital renderings that reveal the intricate beauty of life's machinery. By applying these ten simple rules—from studying the masters to matching representations to messages—researchers can create visualizations that not only accurately represent structural data but also communicate scientific insights with clarity and impact.
The power of effective biomolecular visualization extends far beyond creating attractive images. As the cryo-EM case study demonstrates, the ability to see molecular structures in detail directly advances our understanding of disease mechanisms and therapeutic development. In the words of Dr. DeCaen, "While the Human Genome Project helped to enumerate genetic components, this new technology defines their structural protein products and their location within cells to elucidate how we approach therapeutics" 5 .
As technology continues to advance, the future of biomolecular visualization promises even greater integration of data sources, more intuitive interaction paradigms, and increasingly powerful AI-assisted design. Through continued attention to both the science and art of molecular graphics, researchers will keep unveiling the breathtaking complexity of the molecular world—one carefully crafted image at a time.
Visualizing the Invisible
Biomolecular graphics transform abstract data into intuitive understanding, bridging the gap between molecular structure and biological function.