• Philippe Youkharibache, Philippe Youkharibache, National Cancer Institute

Molecular graphics has been in development for 60 years through the emergence of innovative research and computer technologies one after the other that converged and intertwined over the years to lead us to iCn3D today as a web-based biomolecular graphics platform. 3D Molecular graphics is indissociable of the field protein structure prediction both scientifically and technologically.

It is the first visionary open data resource -the Protein Data Bank - that has been essential for sharing information between scientists in academia, government and industry labs for over five decades. It is the CASP initiative critical assessment of structure prediction that opened communication between scientists in structure prediction to lead, after more than two decades, to the emergence of AlphaFold2.

We have with us today scientists who contributed deeply to the field for decades as well as a scientist from organizations that have been and are at the center of data sharing, and scientists involved in chemistry and biology education.

We will be envisioning how to go from open data to open-source software to open science.

We are back to the future in that respect.

• Barry Honig

The PrePPI algorithm is unique in its ability to predict whether and how two proteins interact on a proteomic scale. PrePPI considers all 200 million possible PPIs in the human proteome and over a million high confidence predictions appear in its online database. PrePPI is based primarily on the use of structural alignment to identify templates in the PDB for homology modeling of complexes but incorporates domain-peptide interactions and non-structural sources of information as well. Recent additions to PrePPI include ZEPPI, which uses evolutionary information to score protein-protein interfaces as well as deep-learning-based approaches. PrePPI performance will be described and its large-scale perspective will be discussed in the context of slower AlphaFold based approaches.

• John Moult

As science evolves, the old ways of ensuring rigor, particularly the venerable peer-reviewed journal paper system, are breaking down. On the other hand, new technologies are providing opportunities for new approaches and the prospect of more rapid advance. One of these is the community critical assessment experiment. CASP (Critical Assessment of Structure Prediction) was the first and has seen a series of both dead-ends and breakthroughs. In this talk I’ll review some of the stops and starts, with the goal of drawing conclusions about how efficiently the field has moved forward and the strengths and limitations of the approach.

• Jianlin Cheng, Jianlin Cheng, University of Missouri - Columbia
• Alex Morehead, Alex Morehead

Estimating the accuracy of protein structural models is a critical task in protein bioinformatics. The need for robust methods in the estimation of protein model accuracy (EMA) is prevalent in the field of protein structure prediction, where computationally-predicted structures need to be screened rapidly for the reliability of the positions predicted for each of their amino acid residues and their overall quality. Current methods proposed for EMA are either coupled tightly to existing protein structure prediction methods or evaluate protein structures without sufficiently leveraging the rich, geometric information available in such structures to guide accuracy estimation. In this work, we propose a geometric message passing graph neural network referred to as the geometry-complete perceptron network for protein structure EMA (GCPNet-EMA), where we demonstrate through rigorous computational benchmarks that GCPNet-EMA's accuracy estimations are faster and more accurate than baseline state-of-the-art methods for both tertiary and quaternary structure EMA. The source code and data for GCPNet-EMA are available on GitHub (https://github.com/BioinfoMachineLearning/GCPNet-EMA).

• Ravi Abrol

iCn3D is an interactive web-based software for studying molecules in biology. It helps visualize and analyze 3-dimensional (3D) models of molecules like proteins, study how these proteins are built, and how they interact within cells and between cells. What makes iCn3D unique is that it lets people share these models online using special weblinks. This sharing fosters teamwork in biology research and in education and enables collaborative research among scholars as much as citizen science. In education, the sharing allows interactive teaching of biology and chemistry concepts around molecular structure: teachers can exchange course materials and assignments with students who can then turn their assignment back through weblinks. The software is free and already has a large community of users worldwide and a growing community of developers. This project, called iCn3D POSE, aims to: a) scope a self-sustaining open-source ecosystem (iCn3D-OSE); b) create a management organization and a roadmap to transition iCn3D into such an open-source ecosystem; and c) begin building an active collaborative community of users and content developers for a sustainable open-source ecosystem. The ability to access structural models of proteins marks a significant advancement in biology and medicine, enabling researchers and clinicians to delve into molecular structures and propose mechanisms for biological functions and malfunctions, to lead to new ways of understanding and treating diseases. However, analyzing 3D protein structures remains a specialized field, often requiring collaboration with experts in protein structure and modeling to develop accurate hypotheses.

The iCn3D-POSE project aims to facilitate the collaborations by leveraging iCn3D's data-sharing features. Through its web-based platform, iCn3D allows scientists to exchange 3D visual representations of molecules (molecular scenes), comparative structural analyses, and annotations, fostering interaction not only with the 3D structures but also among researchers themselves. In the long term, the project aims to create a collaborative and sustainable ecosystem around iCn3D, involving users, developers, organizations, and experts in various fields. In Phase I, the project aims to engage all the potential stakeholders in research, education, and training (collaborators/developers, users, potential scientific advisors, community at large, etc.) in the public and in the private sector, through conference sessions, workshops, hackathons, and interviews. This collaboration will help develop a robust, well-informed, and sustainable plan for the successful development of the open-source ecosystem. By empowering a dynamic community, the iCn3D POSE project holds the potential to drive transformative advancements in education and in research and lead to new ways of understanding biology and diseases at the molecular level.

• Aron Marchler-Bauer

NCBI's Conserved Domain Database was developed with the goal of increasing the coverage and specificity of protein family model-based genome annotation. In reviewing conserved domain families, 3D structure information has been used explicitly to delineate domain extent and construct multiple sequence alignments centered around structurally conserved segments for diverse protein domain superfamilies. The 3D structure viewer Cn3D has been integrated into a curation infrastructure that utilizes pre-computed results of large-scale structure comparisons by VAST (Vector Alignment Search Tool). These results are readily available via Cn3D's successor, iCn3D, which is not tethered to Cn3D's rigid data model and is a vital part of the CDD curation effort as it facilitates comparative analysis of predicted protein structure, which provides functional clues for a large fraction of uncharacterized protein families.

• Chris Henn, Chris Henn, Inside Reality

• Marcus De Almeida Mendes

• Sandra Porter, Sandra Porter, Digital World Biology

Molecular modeling programs, such as iCn3D, are increasingly being used in the classroom. Enhancements to accessibility and usability are contributing to adoption. Two such enhancements are color keys and collections. Color keys help both students and instructors interpret visual information in molecular structure models without having to hunt down user manuals. Collections make it possible for instructors to gather related models together and provide them to students to support online laboratory investigations. We will discuss examples of using collections to facilitate studying drug resistance in influenza, identifying secondary structure elements in antifreeze proteins, identifying common features of immunoglobulins and T cell receptors, identifying where molecules bind DNA, understanding how mutations can lead to breast cancer, and more.

• Jiyao Wang

It’s challenging to understand 3D structural data. To address this, the web-based iCn3D (I-see-in-3D) viewer uses all kinds of 3D, 2D, and 1D views to make this process easy. Specifically, iCn3D simplifies the 3D structural view, reduces 3D view into synchronized 2D cartoon/2D interaction network and 1D tracks of annotations, show side by side 3D structure alignment and the corresponding 1D sequence alignment, displays 3D structures with 3D printing, Virtual Reality (VR) or Augumented Reality (AR), and outputs annotations with Node.js/Python scripts. Furthermore, all iCn3D views can be reproduced in a sharable URL or iCn3D PNG image. The source code of iCn3D is at https://github.com/ncbi/icn3d.

• Henry Jakubowski

Molecular structures determine the properties and functions of molecules throughout chemistry, biology, and their integrated disciplines, yet the lack of routine educational use of computer modeling of molecules is a barrier to student learning. I will explore the use of iCnD to address this deficit.
Static structures populate books but they are inadequate to convey 3D and dynamic properties of chemical structures. iCn3D is unparalleled in offering users (both instructors and students) the ease, utility, and low cost of displaying molecules and their information-rich alternative renderings in service of student learning and its formative and summative assessment. Fundamentals of Biochemistry, a free LibreText OER, with over 600 embedded iCn3D pre-rendered models and associated textual explanations is a prime example of a resource that offers students an integrated learning platform to understand biochemistry structures and their functions.
Yet this resource covers just a small niche of potential users at all levels of biology and chemistry education. We need to promote the use of iCn3D not just in isolated courses but widely in both secondary and undergraduate biology and chemistry classes to make structure/function a fundamental component of all relevant courses. A drive to do this would have the secondary effect of bridging the “cultural divide” that can be found between biology and chemistry departments arising from different training, interests, and perspectives. This divide can compartmentalize, separate, and interfere with integrated learning of structure throughout students’ educational experience. This divide can also be found within departments when routine use of computer-based modeling is siloed in biochemistry courses. This talk is focused on discussing the integrated use of iCn3D in biology and chemistry classes to increase students’ understanding of the critical threshold concept of molecular structure/function.

• Jose Duarte

We will present the latest developments from the RCSB Protein Data Bank organization in relation to its main web portal RCSB.org. The portal now integrates > 1M Computed Structure Models, calculated by AI methods, alongside the entire corpus of experimental data from the PDB. Thus providing access to all of Structural Biology under a single resource.

• Marcelo Querino Lima Afonso, Marcelo Querino Lima Afonso, EMBL-EBI
• Paulyna Magana, Paulyna Magana, EMBL-EBI
• Pdbe-Kb Consortium , Pdbe-Kb Consortium , EMBL-EBI

• Philippe Youkharibache, Philippe Youkharibache, National Cancer Institute

The project named iCn3D POSE (Pathway to an Open Source Ecosystem) holds the potential to drive transformative advancements in education and in research and lead to new ways of understanding biology and diseases at the molecular level, provided we empower a dynamic community.

The ability to access structural models of proteins marks a significant advancement in biology and medicine, enabling researchers and clinicians to delve into molecular structures and propose mechanisms for biological functions and dysfunctions, to lead to new ways of understanding and treating diseases. However, analyzing 3D protein structures remains a specialized field, often requiring collaboration with experts in protein structure and modeling to develop accurate hypotheses.

We developed an initial web-based platform (iCn3D) to allow scientists to exchange 3D visual representations of molecules (molecular scenes), to exchange comparative structural analyses and annotations to foster interaction not just with the 3D structures on a screen, but to foster interaction among researchers themselves.

This panel discussion is about how to begin building an active collaborative community of users and content developers for a sustainable open-source ecosystem involving users, developers, organizations, and experts in biology and chemistry research, education, and training in the public and in the private sector.

• Allissa Dillman

A hackathon is a collaborative event where researchers, software engineers, and coders converge to solve problems creatively in a dynamic setting. These events foster rapid brainstorming and prototyping, extending a tool's functionalities beyond its original design. Thanks to the diverse backgrounds of participants, creative new features can make tools more effective for a wider range of users. iCn3D, a web-based molecular visualization tool by NCBI, is an excellent example of hackathon-driven iteration. Come learn more about iCn3D and the role of hackathon-based tool development!

• Alexa Salsbury

Target Audience: This workshop is designed for the 2024 International Conference on Intelligent Systems for Molecular Biology (ISMB). Tailored for biochemists and molecular biologists with beginner to intermediate familiarity in structural biology, the workshop is applicable to a diverse range of users including students, educators, researchers, and bioinformatics specialists who want to incorporate 3D structure, NCBI tools, and comparative analysis in their work.

Workshop Description: Our workshop offers biochemists and molecular biologists at various educational stages the opportunity to explore and better understand biomolecular structures using NCBI's free, web-based iCn3D tool. Participants will gain insights into different aspects of biomolecular structures, such as motifs, domains, 3D analysis, and comparisons between AlphaFold and PDB files. The workshop primarily focuses on practical applications for researchers and educators while offering valuable insights into integrating structural work with NCBI's extensive
Workshop Details: https://www.nlm.nih.gov/ncbi/workshops/2024-07_ISMBHackathon-3d-molecular-structures/workshop-details.html