About Hemolytic peptides


What are Hemolytic Peptides?

Hemolytic peptides are short chains of amino acids that can disrupt red blood cell (RBC) membranes, leading to cell rupture — a process known as hemolysis. These peptides are often found in nature, such as in snake venoms, antimicrobial peptides, or human immune proteins.



How is This Useful in Therapeutics?

Predicting and controlling hemolytic activity supports multiple therapeutic advancements:

  • Antimicrobial Peptides (AMPs): Non-hemolytic AMPs combat drug-resistant bacteria without harming human cells.
  • Cancer Therapy: Some hemolytic peptides selectively target cancer cells — modifying them improves safety.
  • Drug Delivery: Hemolytic peptides can enhance drug delivery across membranes when tuned to target diseased cells specifically.
  • Antiviral and Anti-fungal Peptides: Safer, modified peptides can fight viruses or fungi without harming human cells.


Hemolytic Peptides: Action Mechanisms


1. Carpet Model

Peptides cover the membrane surface like a carpet. When a critical concentration is reached, the membrane disintegrates.

Example: Cecropins (insects)

Analogy: Like detergent breaking down grease — the membrane dissolves.

3. Detergent-Like Mechanism (Lysis by Micellization)

Peptides integrate into the membrane, causing phospholipids to rearrange into tiny vesicles (micelles), destabilizing the membrane.

Example: LL-37 (human antimicrobial peptide)

Analogy: Like shaking an oil-water mix until droplets form, breaking the structure.

3. Pore Formation (Barrel-Stave Model)

Peptides align parallel to the cell membrane, then insert themselves perpendicularly to form a cylindrical pore. This allows ions and water to flow uncontrollably, leading to cell lysis.

Example: Melittin (bee venom)

Analogy: Like drilling a hole in a balloon — the contents spill out, causing collapse.

4. Toroidal Pore Model

Peptides bend the membrane itself, pulling the lipid heads inward to form a pore. The membrane and peptides intertwine in the structure.

Example: Magainins (amphibians)

Analogy: Like stretching a rubber band until it folds inward to form a hole.


Mechanism of Action of ACP


Why This Matters for Therapeutics

Understanding these mechanisms helps design safer peptides:

  • Pore-forming peptides: Can be modified to selectively target cancer or bacterial cells.
  • Carpet-like peptides: Can be engineered to avoid damaging human cells.
  • Toroidal model peptides: Provide insights into creating peptides that penetrate tough bacterial membranes while sparing human ones.

MAP Format


What is MAP Format?

MAP (Modified Amino acid Peptide) format is a structured representation specifically designed for modified peptides, particularly those containing non-natural residues or chemical modifications that aren't covered by standard one-letter amino acid codes. This format ensures consistency in representing peptide sequences across different computational tools and databases.

Why is MAP Format Important?

In peptide-based therapeutics and bioinformatics, especially when working with hemolytic peptides, accurate representation of both natural and non-natural residues is crucial. MAP format provides a reliable way to encode these sequences for computational analysis, predictive modeling, and database storage.

Need to Convert Your Sequences?

If you have raw peptide sequences and want to convert them into MAP format, you can easily do so using the tools and guidelines provided in the MAP repository developed by Raghava's group. This resource includes conversion utilities, examples, and detailed documentation to help you get started.

Explore the MAP Repository: https://webs.iiitd.edu.in/raghava/maprepo/

Dive deeper into MAP format structure, guidelines for representing modified residues, and how to use MAP files in peptide analysis workflows.

Browse

This section provides information about browsing the Hemolytik 2.0 entries by different ways.

Browse by Source

Users can browse different sources of peptides or proteins.

Browse Proteins

Browse by Function

Users can browse the function of hemolytic peptides. It lists the number of entries of linear and cyclic peptides, the stereochemistry of peptides, and the number of non-hemolytic peptides.

Browse Proteins

Browse by Nature

Users can browse the unique hemolytic peptides by their nature. It lists the number of entries for different nature of peptides.

Browse Peptides

Browse by Length

Users can browse hemolytic peptides in Hemolytik 2.0 based on their length. Sequences up to 40 amino acids are classified as peptides, while those exceeding 40 amino acids are classified as proteins.

Browse Length

Peptide Card

The peptide card contains all the information about a given peptide or protein. The peptide card contains the Basic Information such as PMID, origin, Sequence, Length etc., Information about Modifications such as Chemical Modifications, C-Ter Modifications, N-Ter Modifications, Experimental Data such as Activity, Assay, Cell Line etc., Literature Information such as Title of the paper, DOI, Journal, Abstract etc., Secondary Infromation (DSSP and SMILES) and External Links to PDB, SwissProt or TrEMBL.

The peptide and protein structures present in Hemolytik 2.0 includes both structures from PDB (experimental) and Predicted Structures. The structures also contains some associated data.

  • DSSP States
  • SMILES
For each structure present in PDB, the PDB ID is given in the external links. The predicted structures are predicted using PepStr and PepStrMod Server.

Peptide Card of a Entry in Hemolytik 2.0
Browse Modifications
3D Structure
Browse Modifications

Tools

This section provides information about the tools available in Hemolytik 2.0.

BLAST

Users can run a BLAST query against the Hemolytik 2.0 database. After submission of job it returns the list of peptides similar to the query peptide. The server also provides options to choose different parameters like weight matrix and expectation value.

BLAST Help

BLAST Result

Str_Aln Help

Smith-Waterman Search

Users can run a Smith-Waterman search query against the Hemolytik 2.0 database. After submission of job it returns the list of peptides.

SW Help

Smith-Waterman Result

Str_Aln Help

Mapping

User can select either SuperSearch to search for query PROTEIN sequence against peptides of Hemolytik 2.0 or select SubSearch to search for query PEPTIDE sequence against the peptides of Hemolytik 2.0.

Mapping Help

Mapping Result

Str_Aln Help

Structure Alignment

User can align their PDB structure with any of the Hemolytik 2.0 Structures

Str_Aln Help

Alignment Result

Str_Aln Help

API

This section describes how this website's data can be accessed with programs. A variety of data available on Hemolytik 2.0 is accessible using simple URLs (REST) that can be used in programs.
The Hemolytik 2.0 REST API returns the response in JSON (JavaScript Object Notation) format. Users can parse the JSON format to suit their requirements.

HTTP Status Headers

Upon sending a request to the server the following HTTP response headers are returned by the Hemolytik 2.0 REST API:

Code Description
200 The request was processed successfully.
400 Bad Request. Invalid data type.
404 Not Found. The requested data doesn't exist.
500 Internal server error. Most likely a temporary problem, but if the problem persists please contact us.

Query Fields

The Hemolytik 2.0 REST API offers access to the data through three distinct query fields: source, nature, and peptide sequence. Users can select from a diverse array of options within each field, enabling targeted retrieval of relevant data. Specifically, the nature query field encompasses 5 distinct nature parameters, while the source query field provides access to data from 12 different cell lines, contingent upon their significance within the database. Furthermore, the peptide sequence query field allows users to refine their search based on two parameters: Natural or Modified.

Query Field (..dataType) Parameter (..dataValue) Description
Source Human, Rat, Mouse, Fish, Sheep, Rabbit, Horse, Pig, Chicken, Porcine, Mus musculus, etc. User can access data corresponding to particular source, this will return all the entries for the selected source.
Nature Antimicrobial,Anticancer, Antifungal, Cytotoxic,CPP, etc. User can access data corresponding to particular nature, this will return all the entries for the selected nature.
Peptide Sequence (seq) Natural, Modified Users can access data based on their selectedq parameter. Selecting "Natural" will retrieve entries featuring sequences composed solely of natural amino acid residues, and devoid of any chemical modifications. Conversely, selecting "Modified" will retrieve entries characterized by sequences containing non-natural residues or having any chemical modifications.

Return Fields

Once the request has been processed successfully, the Hemolytik 2.0 REST API returns the data in JSON format. The response data consists of 16 fields:

Return Field Description
ID Unique identifier in the Hemolytik 2.0 database for that entry.
PMID Article PMID corresponding to that entry.
Year Year of publication of that entry.
Sequence Sequence of the peptide.
Name Name of the peptide.
C-Ter Modifications Whether the C-terminal end of the peptide contains an entity or it is free.
N-Ter Modifications Whether the N-terminal end of the peptide contains an entity or it is free.
Linear/Cyclic Conformation of the peptide.
Stereo-chemistry Stereo-chemistry of the peptide.
Chemical Modifications Whether the peptide contains any non-natural residues or any other chemical modifications.
Length Length of the peptide.
Nature Nature of the peptide.
Source The source of peptide used to measure the activity of peptide.
Origin Origin of the peptide corresponding to that source.
Experimental Structure The experimental structure of the peptide.
Non-Hemolytic Whether the peptide is hemolytic or non-hemolytic.

CURL

cURL, short for "Client URL," is a command-line tool and library for transferring data with URLs. It supports a wide range of protocols, including HTTP, HTTPS, FTP, FTPS, SCP, SFTP, LDAP, TFTP, and many others. Example Command:

curl -X GET "https://webs.iiitd.edu.in/hemolytik2/api/api.php?dataType=source&dataValue=Human"
-X flag is used to specify the HTTP request method. HTTP requests typically use methods such as GET, POST, PUT, DELETE, etc. Hemolytik 2.0 REST API allows only GET request method.

wget

wget is a command-line utility for downloading files from the web. It supports downloading files via HTTP, HTTPS, and FTP protocols in Linux environments. Example Command:

wget "https://webs.iiitd.edu.in/raghava/hemolytik2/api/api.php?dataType=source&dataValue=Human"

How to use ?

To access the data programmatically using Hemolytik 2.0 REST API, user simply needs to select the query field and its corresponding query term and hit "Execute".

API Help1

After clicking "Execute" the output will contain the cURL command, wget command, request URL and the server response.

API Help2

Python Example

Below is a very simple example of how to use the Hemolytik 2.0 REST API using Python. It sends a GET request to the API endpoint, retrieves the JSON response containing data, and parses it into a pandas DataFrame for further analysis. This example demonstrates the basic process of accessing data from the Hemolytik 2.0 REST API and manipulating it within a Python environment.

import requests
import pandas as pd

# Define the URL for the API request
url = 'https://webs.iiitd.edu.in/raghava/hemolytik2/api/api.php?dataType=source&dataValue=Human'

# Send a GET request to the API
response = requests.get(url)

# Check if the request was successful (status code 200)
if response.status_code == 200:
    # Print the JSON response from the API
    print(response.json())

    # Parse the JSON data and store it in a pandas DataFrame
    json_data = response.json()
    df = pd.DataFrame(json_data['data'])

    # Visualize the DataFrame
    print(df.head())  # Display the first few rows of the DataFrame

else:
    # Print an error message if the request was not successful
    print('Error:', response.status_code)