Molecular Dynamics Simulations of Membrane Proteins: An Overview

Abstract

Simulations of membrane proteins have been rising in popularity in the past decade. Advancements in technology and force fields made it possible to simulate behavior of membrane proteins. Membrane protein simulations can now be used as supporting evidence for experimental findings, for elucidating protein mechanisms, and validating protein crystal structures. Unrelated to experimental data, these simulations can also serve to investigate larger scale processes like protein sorting, protein–membrane interactions, and more. In this review, the history as well as the state-of-the-art methodologies in membrane protein simulations will be summarized. An emphasis will be put on how to set up the system and on the current models for the different components of the simulation system. An overview of the available tools for membrane protein simulation will be given, and current limitations and prospects will also be discussed.

Deciphering collaborative sidechain motions in proteins during molecular dynamics simulations

“…Focusing on the consensus angles from the first component, we can note that eight out of the ten angles rotamerized within a short time window from 76 to 88 ns, immediately before or during the opening motion of TM6. The only exceptions to this pattern were the dihedral angles of W195 5 . 34 , whose rotation was delayed by about 25 ns.…”

“…This analysis highlighted a few angles clearly separated along the first three principal components. In both cases, the dihedral angles H203 5 . 42 .chi1 and N119 3 .…”

“…For both methods, the top pair with the highest score involved the chi1 angles of N119 3 . 35 and H203 5 . 42 .…”

“…CIRCULAR displayed a main network, with a strong link between N119 3 . 35 and H203 5 . 42 (with 6 common contacts out of a total of 9 and 7 contacts, respectively), but also a secondary network around the chi1 angle of W252 6 .…”

“… 48 . OMES favored an overwhelming, hub-like network with central H203 5 . 42 (13 contacts), strongly linked to N119 3 .…”