How to Design Peptides.

Journal: Methods in molecular biology (Clifton, N.J.)
Published Date:

Abstract

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.

Authors

  • Joseph Dodd-O
    Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
  • Amanda M Acevedo-Jake
    Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
  • Abdul-Rahman Azizogli
    Department of Biology, New Jersey Institute of Technology, Newark, NJ, USA.
  • Vikram Khipple Mulligan
    Center for Computational Biology, Flatiron Institute, New York, USA.
  • Vivek A Kumar
    York Center for Environmental Engineering and Science, New Jersey Institute of Technology, Newark, NJ, USA. vak@njit.edu.