EventsThe 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics
Event submissions
Published
This submission belongs to the session S2. General of the event The 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics
Published date
28 Oct, 2026
Academic Editor
author-avatarMary J. Meegan
Contribution&Funding
Methodology,
[Romeo Karaputadze] ; [Malak Pirtskhakava]
Software,
[Romeo Karaputadze] ; [Mindia Chubinidze]
Validation,
[Evgenia Alimbarashvili] ; [Romeo Karaputadze] ; [Natia Samsonidze] ; [Maia Grigolava]
Formal analysis,
[Natia Samsonidze]
Investigation,
[Maia Grigolava] ; [Evgenia Alimbarashvili]
Resources,
[Maia Grigolava] ; [Malak Pirtskhakava]
Data curation,
[Maia Grigolava] ; [Malak Pirtskhakava]
Writing - original draft,
[Evgenia Alimbarashvili]
Writing - review,
[editing] ; [Evgenia Alimbarashvili]
Visualization,
[Natia Samsonidze]
Supervision,
[Malak Pirtskhakava]
Project administration,
[Malak Pirtskhakava] ; [Evgenia Alimbarashvili]
Funding acquisition,
[Malak Pirtskhakava]
Funding: Shota Rustaveli National Science Foundation of Georgia [Grant number FR-25-412]. International Science and Technology Center [G-2102].
Citation
Romeo Karaputadze, Malak Pirtskhakava, Maia Grigolava, Evgenia Alimbarashvili, Natia Samsonidze, Mindia Chubinidze, PepSMILES: SMILES Generator for Chemically Modified and Cyclized Peptides, in Proceedings of The 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics, 1 November–30 November 2026, MDPI: Basel, Switzerland
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PepSMILES: SMILES Generator for Chemically Modified and Cyclized Peptides

Romeo Karaputadze 1
Malak Pirtskhakava 1
Maia Grigolava 1
Evgenia Alimbarashvili 1
Natia Samsonidze 1
Mindia Chubinidze 1
1. Ivane Beritashvili Center of Experimental Biomedicine, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, 0160, Georgia
Abstract

Chemically modified peptides are promising therapeutic scaffolds, but their database annotations and sequential labeling or adding metadata to raw data, so a machine learning model can learn from it remains difficult. Many peptides consist of features like non-proteinogenic residues, terminal derivatization, macrocyclization, and covalent links between chains. Chemical structure annotations of such modified peptides are only partly covered by existing sequence-to-structure tools.

We developed a Python application PepSMILES[1] that constructs atom-resolved molecular graphs from structured peptide records and exports stereochemical SMILES, V2000 MOL files, and two-dimensional images. The application currently includes more than 650 unusual-amino-acid blocks, together with 370 curated N- and C-terminal modifications. It supports up to 50 intrachain annotations found in the current DBAASP export and nine interchain annotations, including disulfide, amide, ester, thioether, carbon–carbon, heterocyclic, and multibridge closures. Assembly is metadata-driven: each residue and terminal template identifies the atoms involved in peptide or cross-link formation and any leaving groups, while chemistry-specific rules apply the required bond changes for each intra- or interchain modification. When applied at database scale, the workflow returned SMILES for 25,243 of 25,306 eligible DBAASP[2] records. 

Applications like p2smi[3], cyclicpeptide[4], and PepLink[5], none reports this same combination of unusual-residue coverage, terminal derivatization, chemically diverse cyclization, and covalent multimer assembly.  

By reducing manual structure drawing and taking advantage of reusable chemical rules, the application can shorten dataset preparation, improve structural consistency, and allow experimentally described peptides to be compared directly with small molecules in established drug-discovery pipelines. 

This approach makes chemically complex peptides accessible to cheminformatics, QSAR, virtual-screening, and machine-learning workflows.

1. https://dbaasp-dev.ibrsp.org/tools?page=smiles-generator
2. https://dbaasp.org/home
3. https://github.com/AaronFeller/p2smi
4. https://github.com/dfwlab/cyclicpeptide
5. https://github.com/DragonDescentZerotsu/PepLink

Keywords
modified peptides
molecular graph assembly
SMILES
peptide cyclization
cheminformatics
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