Treffer: StaPep: An Open-Source Toolkit for Structure Prediction, Feature Extraction, and Rational Design of Hydrocarbon-Stapled Peptides.

Title:
StaPep: An Open-Source Toolkit for Structure Prediction, Feature Extraction, and Rational Design of Hydrocarbon-Stapled Peptides.
Authors:
Wang Z; Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.; Hangzhou VicrobX Biotech Co., Ltd., Hangzhou 310018, China., Wu J; Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, China., Zheng M; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Geng C; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Zhen B; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Zhang W; Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.; Hangzhou VicrobX Biotech Co., Ltd., Hangzhou 310018, China., Wu H; Huadong Medicine Co., Ltd., Hangzhou 310015, China., Xu Z; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Xu G; Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China., Chen S; School of Medicine, Shanghai University, Shanghai 200444, China., Li X; School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Source:
Journal of chemical information and modeling [J Chem Inf Model] 2024 Dec 23; Vol. 64 (24), pp. 9361-9373. Date of Electronic Publication: 2024 Nov 06.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: American Chemical Society Country of Publication: United States NLM ID: 101230060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-960X (Electronic) Linking ISSN: 15499596 NLM ISO Abbreviation: J Chem Inf Model Subsets: MEDLINE
Imprint Name(s):
Original Publication: Washington, D.C. : American Chemical Society, c2005-
MeSH Terms:
Hydrocarbons*/chemistry , Peptides*/chemistry , Drug Design* , Software*, Models, Molecular ; Protein Conformation ; Machine Learning
Substance Nomenclature:
0 (Hydrocarbons)
0 (Peptides)
Entry Date(s):
Date Created: 20241106 Date Completed: 20241223 Latest Revision: 20241223
Update Code:
20250114
DOI:
10.1021/acs.jcim.4c01718
PMID:
39503524
Database:
MEDLINE

Weitere Informationen

All-hydrocarbon stapled peptides, with their covalent side-chain constraints, provide enhanced proteolytic stability and membrane permeability, making them superior to linear peptides. However, tools for extracting structural and physicochemical descriptors to predict the properties of hydrocarbon-stapled peptides are lacking. To address this, we present StaPep, a Python-based toolkit for generating 3D structures and calculating 21 features for hydrocarbon-stapled peptides. StaPep supports peptides containing two non-standard amino acids (norleucine and 2-aminoisobutyric acid) and six non-natural anchoring residues (S3, S5, S8, R3, R5, and R8), with customization options for other non-standard amino acids. We showcase StaPep's utility through three case studies. The first generates 3D structures of these peptides with a mean RMSD of 1.62 ± 0.86, offering essential structural insights for drug design and biological activity prediction. The second develops machine learning models based on calculated molecular features to differentiate between membrane-permeable and non-permeable stapled peptides, achieving an AUC of 0.93. The third constructs regression models to predict the antimicrobial activity of stapled peptides against Escherichia coli , with a Pearson correlation of 0.84. StaPep's pipeline spans data retrieval, structure generation, feature calculation, and machine learning modeling for hydrocarbon-stapled peptides. The source codes and data set are freely available on Github: https://github.com/dahuilangda/stapep_package.