Coarse-grained modeling of the intrinsically disordered protein Histatin 5 in solution: Monte Carlo simulations in combination with SAXS

Proteins. 2016 Jun;84(6):777-91. doi: 10.1002/prot.25025. Epub 2016 Mar 16.

Abstract

Monte Carlo simulations and coarse-grained modeling have been used to analyze Histatin 5, an unstructured short cationic salivary peptide known to have anticandidical properties. The calculated scattering functions have been compared with intensity curves and the distance distribution function P(r) obtained from small angle X-ray scattering (SAXS), at both high and low salt concentrations. The aim was to achieve a molecular understanding and a physico-chemical insight of the obtained SAXS results and to gain information of the conformational changes of Histatin 5 due to altering salt content, charge distribution, and net charge. From a modeling perspective, the accuracy of the electrostatic interactions are of special interest. The used coarse-grained model was based on the primitive model in which charged hard spheres differing in charge and in size represent the ionic particles, and the solvent only enters the model through its relative permittivity. The Hamiltonian of the model comprises three different contributions: (i) excluded volumes, (ii) electrostatic, and (iii) van der Waals interactions. Even though the model can be considered as gross omitting all atomistic details, a great correspondence is obtained with the experimental results. Proteins 2016; 84:777-791. © 2016 Wiley Periodicals, Inc.

Keywords: Monte Carlo simulations; antimicrobial activity; cationic protein; small angle X-ray scattering; unstructured proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Histatins / chemistry*
  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Models, Biological
  • Monte Carlo Method
  • Osmolar Concentration
  • Protein Conformation
  • Scattering, Small Angle
  • Static Electricity
  • X-Ray Diffraction

Substances

  • HTN3 protein, human
  • Histatins
  • Intrinsically Disordered Proteins