TY - JOUR
T1 - Improved Parameterization of Phosphatidylinositide Lipid Headgroups for the Martini 3 Coarse-Grain Force Field
AU - Borges-Araújo, Luís
AU - de Souza, Paulo Cesar Telles
AU - Fernandes, Fábio
AU - Melo, Manuel N.
N1 - Funding Information:
The authors thank S. Thallmair for critical discussion during parameter development. L.B.-A. thanks the Medical Biochemistry and Biophysics Doctoral Program (M2B-PhD) and Fundação para a Ciência e a Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) for PhD fellowship PD/BD/137492/2018. M.N.M. thanks FCT-MCTES for the “scientific employment stimulus” program CEECIND/04124/2017. M.N.M. also acknowledges FCT for the funding project MOSTMICRO-ITQB, with references UIDB/04612/2020 and UIDP/04612/2020.
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2022/1/11
Y1 - 2022/1/11
N2 - Phosphoinositides are a family of membrane phospholipids that play crucial roles in membrane regulatory events. As such, these lipids are often a key part of molecular dynamics simulation studies of biological membranes, in particular of those employing coarse-grain models because of the potential long times and sizes of the involved membrane processes. Version 3 of the widely used Martini coarse-grain force field has been recently published, greatly refining many aspects of biomolecular interactions. In order to properly use it for lipid membrane simulations with phosphoinositides, we put forth the Martini 3-specific parameterization of inositol, phosphatidylinositol, and seven physiologically relevant phosphorylated derivatives of phosphatidylinositol. Compared to parameterizations for earlier Martini versions, focus was put on a more accurate reproduction of the behavior seen in both atomistic simulations and experimental studies, including the signaling-relevant phosphoinositide interaction with divalent cations. The models that we develop improve upon the conformational dynamics of phosphoinositides in the Martini force field and provide stable topologies at typical Martini time steps. They are able to reproduce experimentally known protein-binding poses as well as phosphoinositide aggregation tendencies. The latter was tested both in the presence and absence of calcium and included correct behavior of PI(4,5)P2 calcium-induced clusters, which can be of relevance for regulation.
AB - Phosphoinositides are a family of membrane phospholipids that play crucial roles in membrane regulatory events. As such, these lipids are often a key part of molecular dynamics simulation studies of biological membranes, in particular of those employing coarse-grain models because of the potential long times and sizes of the involved membrane processes. Version 3 of the widely used Martini coarse-grain force field has been recently published, greatly refining many aspects of biomolecular interactions. In order to properly use it for lipid membrane simulations with phosphoinositides, we put forth the Martini 3-specific parameterization of inositol, phosphatidylinositol, and seven physiologically relevant phosphorylated derivatives of phosphatidylinositol. Compared to parameterizations for earlier Martini versions, focus was put on a more accurate reproduction of the behavior seen in both atomistic simulations and experimental studies, including the signaling-relevant phosphoinositide interaction with divalent cations. The models that we develop improve upon the conformational dynamics of phosphoinositides in the Martini force field and provide stable topologies at typical Martini time steps. They are able to reproduce experimentally known protein-binding poses as well as phosphoinositide aggregation tendencies. The latter was tested both in the presence and absence of calcium and included correct behavior of PI(4,5)P2 calcium-induced clusters, which can be of relevance for regulation.
UR - http://www.scopus.com/inward/record.url?scp=85122356337&partnerID=8YFLogxK
U2 - 10.1021/acs.jctc.1c00615
DO - 10.1021/acs.jctc.1c00615
M3 - Article
C2 - 34962393
AN - SCOPUS:85122356337
SN - 1549-9618
VL - 18
SP - 357
EP - 373
JO - Journal Of Chemical Theory And Computation
JF - Journal Of Chemical Theory And Computation
IS - 1
ER -