# Multidimensional Decomposition and Ensemble Modeling of Histatin 1 and Its Siblings: Detailing Structure and Biological Function Using an Integrative Approach

## TL;DR

This study compares the structure and function of three histatin peptides and shows how phosphorylation changes Histatin 1's behavior, possibly helping it bind to tooth enamel.

## Contribution

A multidimensional decomposition technique is introduced to analyze histatin conformational changes and their biological implications.

## Key findings

- Phosphorylation of Histatin 1 significantly alters its conformational ensemble.
- Histatin 1's phosphorylation may act as a molecular switch for tooth enamel binding.
- Histatins exhibit distinct killing mechanisms involving self-association and membrane disruption.

## Abstract

Histatins are a family of multifunctional, cationic histidine-rich
saliva peptides. The most prominently represented are Histatin 1,
Histatin 3, and Histatin 5. Despite considerable similarities in primary
structure, the three members are known to display varied antimicrobial
properties and healing abilities. This study aims to provide a detailed
structural comparison of Histatin 1, Histatin 3, and Histatin 5, as
well as a thorough investigation into the variation caused to the
conformational ensemble of Histatin 1 upon phosphorylation. The study
applies molecular dynamics simulation, small-angle X-ray scattering,
circular dichroism, bioinformatics tools, and neutron reflectometry.
A multidimensional decomposition technique and its connection to clustering
methods are also presented. It was observed that the phosphorylation
of Histatin 1 profoundly shifts the conformational ensemble and may
act as a molecular switch that facilitates tooth enamel binding. Observations
are provided on the killing mechanisms of Histatins concerning self-association
and membrane rupturing.