Membrane Protein Dynamics from Femtoseconds to Seconds

Abstract

Membrane proteins play a key role in energy conversion, transport, signal recognition, transduction, and other fundamental biological processes. Despite considerable progress in experimental techniques, the determination of structure and dynamics of membrane proteins still represents a great challenge. Computer simulation methods are becoming an increasingly important tool not only in the interpretation of experiments but also in the prediction of membrane protein dynamics. In the present review, we give a brief introduction to molecular modeling techniques currently used to explore protein dynamics on time scales ranging from femtoseconds to microseconds. We then describe a few recent example applications of these techniques to membrane proteins. In conclusion, we also discuss some of the newest developments in simulation methodology that have the potential to further extend the time scale accessible to explore (membrane) protein dynamics.

Dynamics comparison of two myoglobins with a distinct heme active site

“…As a complimentary approach, molecular dynamics (MD) simulations have become a powerful tool to provide atomic level and time-dependent information for protein structure and functions that otherwise is difficult to obtain from experiments [17][18][19][20][21]. To date, plenty of MD simulations have been performed for swMb to gain insights into its folding behaviors and functioning as an O 2 carrier [21][22][23][24][25][26][27].…”

Computational insight into nitration of human myoglobin

“…Recently, Iniesta and co-workers (Gómez-Mingot et al, 2013) selectively nitrated horse Mb at Tyr103 using an electrochemical approach and performed spectroscopic studies on not pure nitrated Mb, which provides some undirected structural information for nitrated Mb. As a compliment, computational approach such as molecular dynamics (MD) simulation has become a powerful tool to provide atomic level and time-dependent information for protein structure and function that otherwise is difficult to obtain from experiments (Karplus and McCammon, 2002;Daggett, 2006;Sotomayor and Schulten, 2007;Kandt and Monticelli, 2010;Lin, 2011;Lin and Liao, 2011;Lin et al, 2012a). Mb is an ideal protein model for investigating the structure and function relationship of heme proteins in both native and non-native states (Lu et al, 2003Lin et al, , 2014Liu et al, 2014), and computer simulation plays a key role in guiding protein design and engineering based on Mb (Sigman et al, 2000;Yeung et al, 2009;Lin et al, 2012b).…”

Molecular Dynamics Computer Simulations of Multidrug RND Efflux Pumps

“…Proteins are in an ongoing state of motion easily exceeding mere thermal fluctuation and in most cases this conformational dynamics is the foundation enabling a protein to carry out its physiological function in the first place [1, 2]. Part of the molecular mechanical branch of modelling techniques [2], molecular dynamics (MD) simulations numerically investigate the motion of a system of particles under the influence of internal (interactions between atoms) and external forces such as temperature or pressure [3] as well as optional additional forces in steered or targeted MD [4]). A key ingredient of MD simulations is the potential energy function that relates energy to structure using harmonic, periodic, Coulomb and Lennard Jones-like potentials to calculate the forces acting on each particle in the system.…”