Constant pH Molecular Dynamics through λ-dynamics

Constant pH Molecular Dynamics through lambda-dynamics

by Eliane Briand
Cumulative thesis
Date of Examination:2024-10-21
Date of issue:2025-02-26
Advisor:Prof. Dr. Helmut Grubmüller
Referee:Prof. Dr. Ricardo Mata
Referee:Prof. Dr. Marina Bennati
Persistent Address: http://dx.doi.org/10.53846/goediss-11108

 

 

Files in this item

Name:BRIAND_Eliane_thesis_mixed.pdf
Size:31.0Mb
Format:PDF
Description:Thesis document as single PDF file

The following license files are associated with this item:

Abstract

English

This thesis presents a novel implementation of constant pH molecular dynamics simulations using λ-dynamics with Hamiltonian interpolation, enabled by an efficient Fast Multipole Method electrostatic solver. The accuracy of the method was validated against NMR titration data for protein test systems (cardiotoxin V, lysozyme, staphylococcal nuclease ∆PHS). New analysis tools were developed to systematically study protonation-conformation and residue-residue couplings, and applied to the test systems, revealing known as well as new protonation couplings in those proteins. The issue of convergence for residues subject to coupling is raised for constant pH simulations in general.
Keywords: biophysics; simulation; molecular dynamics; protonation; acid base; protein; constant ph; free energy
 
Statistik