iCn3D, a web-based 3D viewer for sharing 1D/2D/3D representations of biomolecular structures

Abstract

Motivation Build a web-based 3D molecular structure viewer focusing on interactive structural analysis. Results iCn3D (I-see-in-3D) can simultaneously show 3D structure, 2D molecular contacts and 1D protein and nucleotide sequences through an integrated sequence/annotation browser. Pre-defined and arbitrary molecular features can be selected in any of the 1D/2D/3D windows as sets of residues and these selections are synchronized dynamically in all displays. Biological annotations such as protein domains, single nucleotide variations, etc. can be shown as tracks in the 1D sequence/annotation browser. These customized displays can be shared with colleagues or publishers via a simple URL. iCn3D can display structure–structure alignments obtained from NCBI’s VAST+ service. It can also display the alignment of a sequence with a structure as identified by BLAST, and thus relate 3D structure to a large fraction of all known proteins. iCn3D can also display electron density maps or electron microscopy (EM) density maps, and export files for 3D printing. The following example URL exemplifies some of the 1D/2D/3D representations: https://www.ncbi.nlm.nih.gov/Structure/icn3d/full.html?mmdbid=1TUP&showanno=1&show2d=1&showsets=1. Availability and implementation iCn3D is freely available to the public. Its source code is available at https://github.com/ncbi/icn3d. Supplementary information Supplementary data are available at Bioinformatics online.

Using iCn3D and the World Wide Web for structure-based collaborative research: Analyzing molecular interactions at the root of COVID-19

“…These URLs are "lifelong" and can be accessed from a preprint or a publication. We started to publish 3D analyses as links 1,6 . This paper further demonstrates its use with links that annotate structures and molecular interactions between SARS-COV-2 and the human ACE2 receptor, or with antibodies.…”

“…This is the 3rd function of iCn3D: providing a capability to share structural analysis and annotations with collaborators and peers and use them in publications. These links are in fact already used today by a number of professors in teaching about protein structure and molecular interactions, and we envision them as being used for peer review and publication, as we have started to do ourselves in our latest preprints and papers 1,6 .…”

“…The HKU1 (PDB 5I08) structure, in the same way shifts by 3 residues strand 1 matching VV Y with the preceding SYD residues, yet strand 2 and the flanking loop are well positioned. Free energy calculations ∆∆G values were computed using the Free Energy Perturbation slow growth calculation approach as described in [1] using Gromacs 5.1.4 [2] and the PMX package [3] considering the "unbound" geometries (instead of the "unfolded" states as described in [1]) The ∆∆G values were computed in the forward and backwards direction. The values reported are the average of the two.…”

“…By contrast, it only takes a second to share a structural annotation worldwide through 3D web links 1 , exactly as one would share a Google map or a Google Doc. For example, a simple link can focus on the SARS-COV-2 Receptor Binding domain interacting with the ACE2 receptor The unprecedented volume of new structures and new sequencing data shared through the Internet as data sets, preprints and publications exacerbates the need to perform structural analyses quickly and share these results with collaborators and through online publications.…”

Identification of the novel HLA allele, HLA‐C*07:780, identified in a Danish woman

“…To assess the impact of the amino acid substitution we identified HLA‐C*07:02 (5VGE) in PDB, as the protein closes to HLA‐C*07:780. A model of the structure was generated using iCn3D with amino acid 49 (alanine) represented in balls‐and‐sticks. Although the substitution is in the peptide binding domain, it is outside the core of the peptide binding groove and it is therefore anticipated to have only a minor effect on peptide binding .…”