How to Design Peptides

Joseph Dodd-o, Amanda M. Acevedo-Jake, Abdul Rahman Azizogli, Vikram Khipple Mulligan, Vivek A. Kumar

Research output: Chapter in Book/Report/Conference proceedingChapter


Novel design of proteins to target receptors for treatment or tissue augmentation has come to the fore owing to advancements in computing power, modeling frameworks, and translational successes. Shorter proteins, or peptides, can offer combinatorial synergies with dendrimer, polymer, or other peptide carriers for enhanced local signaling, which larger proteins may sterically hinder. Here, we present a generalized method for designing a novel peptide. We first show how to create a script protocol that can be used to iteratively optimize and screen novel peptide sequences for binding a target protein. We present a step-by-step introduction to utilizing file repositories, data bases, and the Rosetta software suite. RosettaScripts, an.xml interface that allows for sequential functions to be performed, is used to order the functions for repeatable performance. These strategies may lead to more groups venturing into computational design, which may result in synergies from artificial intelligence/machine learning (AI/ML) to phage display and screening. Importantly, the beginner is expected to be able to design their first peptide ligand and begin their journey in peptide drug discovery. Generally, these peptides potentially could be used to interact with any enzyme or receptor, for example, in the study of chemokines and their interactions with glycosoaminoglycans and their receptors.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Number of pages30
StatePublished - 2023

Publication series

NameMethods in Molecular Biology
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics


  • Bioactive peptide
  • Peptide design
  • Peptide inhibitors
  • Peptide ligand
  • Peptide–protein interaction
  • Rosetta scripts


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