Folding and insertion thermodynamics of the transmembrane WALP peptide

Abstract

A refined polarizable water model for the coarse-grained MARTINI force field with long-range electrostatic interactions The Journal of Chemical Physics 146, 054501 (2017) The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA) n (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum-in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence. C 2015 AIP Publishing LLC. [http://dx

Evaluation of the hybrid resolution PACE model for the study of folding, insertion, and pore formation of membrane associated peptides

“…In comparison to the AA PMFs of WALP16 insertion, it appears PACE is overstabilizing the interfacial state. This same problem was observed in pure MARTINI simulations, although there the interfacial state of WALP16 was globally stable and the barrier separating TM and interfacial states was considerably larger than what we compute for PACE . In the same paper by Bereau et al, they compute an atomistic insertion PMF, which shows a similar barrier between interfacial and TM configurations as we compute in PACE, but the TM state free energy is lower than the interfacial state by ∼7 kcal/mol.…”

“…Atomistic simulations are suited to examine this problem, but differing results have been reported. Unbiased simulations have shown unfolding to occur in solution, while metadynamics simulations have shown both folded and unfolded conformations are thermally accessible and the folded state is the free energy minimum . There is a possibility that PACE is overstabilizing the helical content in the aqueous phase, but it does show that the membrane environment can influence the peptide structure.…”

“…Atomistic simulations using the GROMOS force‐field have been used to compute the PMF of WALP16 insertion into a POPC bilayer . In that calculation, umbrella sampling was used with 200 ns/window sampling along the insertion pathway.…”

Engineering von Proteinen an Oberflächen: Von komplementärer Charakterisierung zu Materialoberflächen mit maßgeschneiderten Funktionen

“…Die Komplexitätvieler biomolekularer Systeme schränkt die Mçglichkeiten von atomaren Simulationen -i nd enen alle Atome explizit dargestellt sind -s elbst mit heutigen Rechenmethoden und Computern stark ein. [106] Das Modell hat ebenfalls gezeigt, dass es in der Lage ist, einfache Sequenzen in der Membran, wie z. Coarse-grained, also systematisch vergrçberte Modelle vereinigen mehrere Atome zu einem grçßeren Partikel oder einer grçßeren Kugel und sorgen dadurch füre ine erhebliche Beschleunigung der Berechnungen.…”

How transmembrane peptides insert and orientate in biomembranes: a combined experimental and simulation study

“…45 They found that only the Martini force field exhibits a pronounced secondary minimum for an interfacial adsorbed state. 45 They found that only the Martini force field exhibits a pronounced secondary minimum for an interfacial adsorbed state.…”