Ateneo - UPO

The course deals with the visual representation of molecules and macromolecules as a tool of scientific communication. It is organized by object to be represented, in order of increasing representational freedom: from the two-dimensional structural formula, where conventions are codified and binding, to the three-dimensional model, the macromolecule and its complex with a ligand, the mechanism-of-action diagram, and finally the graphical abstract. For each object the appropriate tool is used, and a single assigned case (drug and its target) runs through all blocks, producing the materials that come together in the final assignment.

Teaching material provided by the lecturer and available on the D.I.R. platform (http://www.dir.uniupo.it): lecture handouts, step-by-step operating guides for each of the programs used, an annotated collection of examples of figures from the scientific literature indicating what works and what does not, sample scripts, preconfigured rendering scenes and presets, coordinate files and structures used in the exercises.

Normative references and drawing conventions:
- European Pharmacopoeia, graphic conventions adopted in the structural formulae of monographs
- IUPAC recommendations for the graphical representation of stereochemical configuration and of chemical structure diagrams
- Author guidelines and figure requirements of the main journals in the field, collected on D.I.R.

Online resources used during the course:
- Protein Data Bank (https://www.rcsb.org) and its outreach section PDB-101 (https://pdb101.rcsb.org)
- official documentation of the programs used, indicated on D.I.R. with the relevant links

Recommended further reading: D. S. Goodsell, "The Machinery of Life", Springer.

Guidance for exam preparation: for producing the assignment, the operating guides, scripts and presets provided are essential; for the discussion, the handouts and the annotated collection of examples are appropriate.

This elective course contributes to the educational objectives of the single-cycle Master's Degree in Pharmacy by developing a transferable scientific communication competence: the ability to correctly represent and critically read images of molecules, macromolecules and mechanisms of action, which students encounter in the scientific literature, in their final dissertation and in their subsequent professional activity.

Breakdown of credits by type of teaching activity (2 ECTS, 50 total hours):
- lecture-based teaching (DE): 4 hours presenting the contents in the computer room, distributed as the introductory part of each block;
- interactive teaching (DI): 12 hours of exercises at individual workstations, producing outputs, comparing results and engaging in structured peer critique;
- self-study: 34 hours, including individual study and the preparation of the final assignment.

Specific objectives. At the end of the course students are able to:
1. draw the structural formula of a drug in accordance with codified conventions, check its consistency with name, molecular formula and relative molecular mass, and identify errors in a table of structures;
2. build a three-dimensional model of a small molecule, declaring the origin of the conformation represented;
3. retrieve a structural model of a macromolecule, assess its quality and establish what the data allow to be represented;
4. build a figure of a ligand-protein complex compliant with editorial requirements and make it reproducible through scripts;
5. recognize what an advanced rendering engine makes possible and establish when its use is appropriate to the communicative register;
6. represent a mechanism of action as a readable diagram, graphically distinguishing documented steps from simplified or hypothetical ones;
7. assemble heterogeneous materials into a coherent graphical abstract and defend the choices made against reasoned criticism.

No formal prerequisites are required. In order to follow the course profitably, it is useful to have the knowledge acquired in the courses of the first three years of the programme, in particular:
- organic chemistry: representation of structural formulae, recognition of functional groups, stereochemistry and assignment of configuration;
- biochemistry: structure of amino acids and three-dimensional organization of proteins, structure of nucleic acids;
- general notions of medicinal chemistry and pharmacology concerning the interaction between a drug and its target and mechanisms of action.

No previous computing skills are required beyond ordinary use of a personal computer, and no programming experience: the scripting elements needed are introduced during the course starting from elementary operations. No previous graphic design skills are required.

The course is organized in eight two-hour blocks, held in a computer room with one workstation per student. Each block consists of a short lecture-based part, supported by slides and annotated examples from the literature, and of a longer practical part in which each student implements on the computer what has been discussed.

The course is organized by object to be represented: each object has its appropriate tool. A two-dimensional structure editor is used for structural formulae, a molecular builder for three-dimensional models of small molecules, a molecular viewer for macromolecules and complexes, a rendering engine for outreach-quality images, and a scientific illustration platform for mechanism diagrams and final assembly. The block devoted to advanced rendering is demonstrative with a guided exercise: scenes and presets prepared by the lecturer are used, while geometry modelling and node systems are explicitly outside the programme.

A single assigned case, consisting of a drug and its target, runs through all blocks: each produces material that feeds into the final assignment, so that learning the tools serves a unified piece of work rather than a sequence of independent exercises.

The exercises are organized around problems: a communication goal is assigned and each student builds their own solution. The results are compared in class: since different solutions are all technically correct but not equally effective, peer comparison is the means through which the learning outcomes concerning making judgements and communication skills are pursued.

The D.I.R. platform (http://www.dir.uniupo.it) hosts the handouts, the operating guides of each session, the scripts and presets, the files used and a forum moderated by the lecturer. Students who are unable to attend find there the complete guides, which can be run on a personal workstation, and may arrange office-hour meetings dedicated to checking the progress of their assignment.

For further information please refer to the course page on D.I.R. at http://www.dir.uniupo.it

The programs used are partly freely downloadable and installable on a personal workstation, and partly available under academic or institutional licence; access and installation instructions are available on D.I.R. before the beginning of the lectures, so that every activity can be repeated outside class hours.

The competences developed in this course can be directly used in preparing the final dissertation and in presenting structural data and mechanisms of action in scientific and professional contexts.

Students with physical disabilities, Learning Disabilities or Special Education Needs can request specific services and tools via the Staff Sviluppo e Coordinamento Carriere e Servizi alle Studentesse e agli Studenti, consulting the University webpage: https://www.uniupo.it/en/services/services-students-physical-or-learning-disabilities
Students with disabilities, learning disabilities or special education needs, once they have contacted the University Staff, can refer to the lecturer in charge of the course to define the examination modalities, concerning academic aspects.

The examination consists of the presentation and discussion of an individual assignment, namely a graphical abstract concerning the case assigned during the course. The mark is expressed out of thirty.

Submission. The assignment must be submitted at least seven days before the examination date and comprises three elements: the graphical abstract in the required format, the dossier of the intermediate materials produced in the individual blocks (structural formula, three-dimensional model, figure of the complex, render, mechanism diagram) and a one-page justification note declaring the representational choices made and the sources of the data used.

Oral discussion (about twenty minutes). It consists of three parts: (a) presentation of the assignment, with justification of the choices of representation, colour, composition and level of detail; (b) a specific check on the compliance of the structural formula with codified conventions and on the consistency between structure, name and molecular formula; (c) critical comment on a published figure proposed by the lecturer, identifying its strengths and possible ambiguities.

Correspondence between level achieved and mark bands:
- 18-20: produces technically correct and readable outputs complying with the assigned requirements, and describes their own choices in an essential way.
- 21-23: justifies representational choices in relation to the message to be conveyed, and checks the consistency between figure and source data.
- 24-26: complies with codified conventions in drawing the structure, consciously adapts the assignment to audience and medium, and makes their own work reproducible.
- 27-29: integrates heterogeneous materials coherently, graphically distinguishes the different levels of evidence in the mechanism diagram, and independently identifies the ambiguities of someone else's figure.
- 30 and 30 cum laude: produces an original and effective assignment, critically discusses its limitations and supports a reasoned judgement on the representational correctness of complex examples.

The minimum pass level requires the complete submission of the three elements and passing all three parts of the discussion.

The course is organized in eight two-hour blocks, by object to be represented and in order of increasing representational freedom. A single assigned case, a drug and its target, runs through all blocks.

1. The figure as a scientific argument (2 hours). A short history of molecular representation. The four assessment criteria adopted in the course: correctness with respect to the data, readability, representational honesty, communicative effectiveness. The registers of scientific communication and their audiences: the formula of a monograph, the figure of an article, the mechanism diagram, the graphical abstract, the outreach image. The chain of tools and formats, and what is lost at each step. Presentation of the assigned case.

2. The two-dimensional structure and its rules (2 hours). The structural formula as a document with identifying value. The graphic conventions of European Pharmacopoeia monographs: constant bond lengths and angles, standard ring orientation, established templates for steroids, sugars, beta-lactams and peptides. IUPAC recommendations on the representation of stereochemical configuration: position and direction of the wedge, use of the hashed bond, meaning of the wavy bond, ambiguous cases on ring-fusion bonds. Representation of racemates, single enantiomers and mixtures of diastereomers. Salts, hydrates, solvates and zwitterions: components and stoichiometry. Consistency check between drawn structure, name, molecular formula and relative molecular mass. Drawing settings required by journals. Catalogue of recurring errors.

3. The molecule in three dimensions (2 hours). From the flat structure to coordinates: generating the three-dimensional model as a construction. Declared stereochemistry versus stereochemistry assigned by the program. Force-field optimization at a practical level and dependence on the starting point. The conformation represented as a choice to be declared in the caption. Representations of the small molecule and the information each conveys. Measurement of distances, angles and dihedrals and their annotation. Export to the following tools.

4. The macromolecule: source, quality, representation (2 hours). Structural database and archives of predicted models; anatomy of a coordinate file. Quality indicators: resolution, B-factor by region, occupancies, unmodelled regions, alternate conformations, confidence scores of predicted models. Consequences for representation and ways of signalling uncertainty. Logic of selections. Types of macromolecular representation and their implicit meaning. Colour: perceptually correct schemes, accessibility for colour vision deficiencies, chromatic consistency. Rendering depth through background, shadows and ambient occlusion. Visual density and reduction of elements.

5. The complex and the scene (2 hours). The figure of the ligand in the binding site: what to show and what to remove. Molecular and electrostatic surfaces and the mandatory scale. Cavities and pockets. Interactions as the outcome of geometric criteria set in the program; annotation of distances and angles. Framing and reproducible orientation. From the interactive session to the script: structure of a readable script and verification from an empty session. Automation of series of figures. Resolution, vector and raster formats, publishers' requirements.

6. Advanced rendering: what can be done (2 hours). Demonstration block with a guided exercise. What a rendering engine adds: lighting, materials, depth of field, ambient occlusion. Import of a molecular structure through a dedicated add-on. The three parameters that determine the result: light, material, framing. Use of prepared scenes and presets. The illustration of the crowded cellular environment: distinguishing data, inference and illustrative licence. When the use of photorealistic rendering is not appropriate to the register. Costs in time and reproducibility. Geometry modelling and node systems are not part of the programme.

7. The process: from mechanism to diagram (2 hours). The pathway diagram as a causal argument in graphic form. The established iconographic repertoire and the assumptions each symbol induces in the reader. Scale and proportion between entities of incomparable size. Choice of the level of detail and its declaration in the legend. Forms of misleading representation: undemonstrated steps, emphasis not proportional to the evidence, suggested directionality and stoichiometry. Placement and graphic distinction of the drug in the diagram. Chromatic and typographic consistency with the structural figures produced in the previous blocks.

8. The graphical abstract and collective critique (2 hours). Definition and limits of the graphical abstract. Composition: visual hierarchy, entry point, reading path, density and white space. Integration of heterogeneous elements through a common palette, line weights, typography and scale. Typography in figures and minimum legible size in print. Formats and editorial requirements. Structured peer critique according to the four criteria, and final revision of the assignment.

INTEGRATION OF THE GENDER DIMENSION
In the first block about half an hour is devoted to the theme of attribution and recognition in the production of scientific images, starting from the case of the X-ray diffraction of DNA and the role of Rosalind Franklin. In the seventh block, devoted to mechanism diagrams, it is further examined how the iconographic conventions used in biomedical illustration convey undeclared assumptions — from the choice of stylized human figures used to represent patients and experimental subjects, to the default representation of organs and systems — and which measures allow them to be avoided.

Knowledge and understanding. Students know: the codified graphic conventions for representing the structural formulae of drugs and the recommendations on the representation of stereochemistry; the main databases of molecular structures and the quality indicators of a structural model; the types of two-dimensional, three-dimensional and macromolecular representation and the information each conveys or omits; the principles for choosing colour, rendering depth and composing a scientific figure; the main functions of the programs used and the logic of scripting; the iconographic repertoire of mechanism diagrams and the assumptions it induces; image integrity criteria and editorial requirements for scientific figures.

Applying knowledge and understanding. Students are able to: draw a structural formula compliant with the conventions and check its internal consistency; build a three-dimensional model of a small molecule; retrieve and assess a structural model of a macromolecule; build a figure of a ligand-protein complex compliant with assigned requirements and make it reproducible through scripts; obtain an advanced render starting from prepared scenes; build a mechanism-of-action diagram; assemble the materials into a coherent graphical abstract.

Making judgements. Students are able to establish what a structural datum allows to be represented and what it does not; to recognize in a published figure the choices that make it ambiguous or misleading; to distinguish, in a mechanism diagram, documented steps from hypothetical ones; to choose, among solutions that are all technically correct, the most effective one for the intended audience and medium; to judge when the use of photorealistic rendering is appropriate to the register.

Communication skills. Students are able to build an image conveying a stated message to a defined audience; to illustrate and justify their representational choices orally; to formulate and receive reasoned critical comments on a graphic output.

Learning skills. Students are able to learn independently how to use new functions of a program from the official documentation and from examples, and to assess the suitability of a new tool for their purpose.

Minimum pass level: producing technically correct and readable outputs complying with the assigned requirements and describing their choices in an essential but correct way. Advanced level: producing an original and effective assignment, coherently integrating heterogeneous materials, graphically declaring levels of evidence and arguing a reasoned critical judgement on figures produced by others.