pK a Calculations in Membrane Proteins from Molecular Dynamics Simulations

Nuno F B Oliveira; Tomás F D Silva; Pedro B P S Reis; Miguel Machuqueiro

doi:10.1007/978-1-0716-1468-6_11

pK _a Calculations in Membrane Proteins from Molecular Dynamics Simulations

Methods Mol Biol. 2021:2315:185-195. doi: 10.1007/978-1-0716-1468-6_11.

Authors

Nuno F B Oliveira¹, Tomás F D Silva¹, Pedro B P S Reis¹, Miguel Machuqueiro²

Affiliations

¹ BioISI - Biosystems and Integrative Sciences Institute, Faculdade de Ciências da Universidade de Lisboa, Lisboa, Portugal.
² BioISI - Biosystems and Integrative Sciences Institute, Faculdade de Ciências da Universidade de Lisboa, Lisboa, Portugal. machuque@ciencias.ulisboa.pt.

PMID: 34302677
DOI: 10.1007/978-1-0716-1468-6_11

Abstract

The conformational changes of membrane proteins are crucial to their function and usually lead to fluctuations in the electrostatic environment of the protein surface. A very effective way to quantify these changes is by calculating the pK _a values of the protein's titratable residues, which can be regarded as electrostatic probes. To achieve this, we need to take advantage of the fast and reliable pK _a calculators developed for globular proteins and adapt them to include the explicit effects of membranes. Here, we provide a detailed linear response approximation protocol that uses our own software (PypKa) to calculate reliable pK _a values from short MD simulations of membrane proteins.

Keywords: Conformation; Linear response approximation; Lipid bilayer; Monte Carlo; Poisson–Boltzmann; Protonation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Membrane Proteins / metabolism*
Molecular Dynamics Simulation
Protein Conformation
Software
Static Electricity

Substances

Membrane Proteins