Fragment-based Peptide Design Service

At CD ComputaBio, we specialize in designing peptides using a fragment-based approach, specifically modulating key protein-protein interactions (PPIs). Our methodology integrates computational biology technologies and advanced algorithms to accelerate the development of peptide-based therapeutics.

Overview of Computational Fragment-based Drug Design

Computational fragment-based drug design (FBDD) is an evolving field where advanced computational methods screen large, diverse fragment libraries. Fragments are evaluated through virtual screening to identify promising candidates based on hydrogen bonding and hydrophobic interactions. Strategies such as fragment growing, linking, or merging then create lead compounds. Subsequent computational validations and biological assays assess these leads, while methods like X-ray crystallography or NMR confirm binding modes. This process deepens our understanding of receptor-ligand interactions and drives modern drug discovery forward.

Fig. 1 A flowchart of fragment-based drug design. (Li Q., 2020)

Fragment-based Peptide Design Approach

Protein-protein interactions (PPIs) are critical for cellular functions, and their disruption can lead to severe dysfunction. Fragment-based peptide design offers a novel strategy to modulate PPIs by constructing peptides or peptide derivatives. Individual amino acids or peptide fragments are docked onto the target surface, and fragments with favorable binding energies are connected to form peptide sequences and structures. The resulting peptides are further validated using molecular docking and molecular dynamics simulations.

Fig. 2 A fragment-based approach to design cyclic peptides. (Delaunay M, et al., 2023)

Our Services

CD ComputaBio is a globally leading computational biology company committed to providing clients with cutting-edge fragment-based peptide design services. We have an experienced, highly skilled professional team and advanced computational platforms designed to help clients accelerate their research processes.

Workflow of Fragment-based Peptide Design

Binding Pocket Identification

Obtain the three-dimensional structure of the target protein and use molecular surface analysis tools to locate binding sites on the target or potential binding regions.

Fragment Library Docking

Systematic screening of peptide fragments/residue pairs against target pockets to identify optimal interaction motifs. Dock residue pairs or fragments from the fragment library into the target's binding site to identify initial fragments that can effectively interact with the target.

Fragment Assembly

Integrate high-affinity fragments into a complete peptide chain through methods such as fragment growing, fragment linking, or fragment merging.

Computational Validation and Screening

Long-timescale molecular dynamics simulations are used to validate the dynamic stability of peptide-target complexes. MM/GBSA or MM/PBSA methods are used to calculate binding free energies, screening for high-affinity candidate peptides.

Common Strategies for Fragment-based Peptide Design

Fragment-based peptide design can identify interaction sites within the protein-peptide binding process because fragments can interact with specific regions of the target protein. Once the fragments within the binding pocket are identified, they can be grown, linked, or merged to develop a library of potential peptides.

Fragment Growing

Precisely position fragments with affinity for specific subregions within the binding pocket, and skillfully add substituents based on chemical rules to gradually grow and enhance activity.

Fragment Linking

Identify and screen multiple fragments that can simultaneously occupy different subregions of the binding pocket, and use linkers to connect them according to synthesis rules, thereby enhancing drug-likeness.

Fragment Merging

Relying on known lead compounds, comprehensively consider physicochemical properties, binding interactions, and synthetic feasibility to connect appropriate fragments and linkers.

Fragment-based peptide design is transformative in the landscape of drug discovery, providing new possibilities for creating highly specific and effective therapeutics. Partner with CD ComputaBio to harness this innovative technology and advance your peptide research. For inquiries and detailed information about our fragment-based peptide design service, please contact us.

References:

Li, Q. Application of fragment-based drug discovery to versatile targets[J]. Frontiers in molecular biosciences. 2020, 7: 180.
Delaunay, M.; Ha-Duong, T. Computational design of cyclic peptides to inhibit protein-peptide interactions[J]. Biophysical Chemistry. 2023, 296: 106987.

For research use only. Not intended for any clinical use.

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