CgProt Force Field

CgProt is a coarse-grained, implicit solvent force field for molecular dynamics simulations of lipid-protein interactions in the presence of an explicit lipid bilayer. Version 2.4 was validated using the known permeation energetics of the twenty amino acid sidechains in the membrane bilayer.

  • RD Hills Jr. 2018. Refining amino acid hydrophobicity for dynamics simulation of membrane proteins. PeerJ 6:e4230. OpenAccess
PeerJ 2018

Physiological Lipids

Zwitterionic POPC and POPE phospholipids are commonly found in eukaryotic membranes, along with a significant proportion of cholesterol. Prokaryotic membranes contain a majority of POPE with smaller quantities of the anionic, nonlamellar lipids POPG and double phospholipid cardiolipin. Coarse-grained representations enable the simulation of a 20 nm bilayer patch that closely resembles the experimental area per lipid.

  • RD Hills Jr and N McGlinchey. 2016. Model parameters for simulation of physiological lipids. J. Comput. Chem. 37, 1112-18. OpenAccess

Multiscale Model Development

A publication in Methods in Molecular Biology describes the mathematical potentials used to treat forces between interaction centers. Unlike other approaches that assume the Lennard-Jones functional form (e.g. MARTINI), fully flexible tabulated potentials are employed. Improvements to the force field include an improper torsion for maintaining sidechain chirality and a Gaussian double-well network for conformational transitions.

  • RD Hills Jr. 2014. Balancing bond, nonbond and Gō-like terms in coarse grain simulations of conformational dynamics. Methods Mol. Biol. 1084, 123-40. PubMed

Lipid Interactions with Membrane Proteins

Molecular dynamics simulations are performed on the bacterial efflux transporter, MsbA, in context of the lipid bilayer. Linear protein diffusion is observed on the microsecond timescale, a feat not possible with traditional atomistic simulations. Simulation of the open-to-closed transition between ATP-dependent conformations reveals an interplay with the surrounding lipid environment. The local bilayer structure is perturbed and an ordered ring of annular lipids solvate the protein.

  • AB Ward, O Guvench and RD Hills Jr. 2012. Coarse grain lipid-protein molecular interactions and diffusion with MsbA flippase. Proteins 80, 2178-90. PubMed

University of Utah (2008-2010)

Coarse-grained models enable simulation of conformational dynamics on biological timescales that cannot be addressed with traditional atomistic simulation. To develop a force field that can be used for any protein sequence, force matching methodology is employed to construct effective potentials from forces in atomistic simulations of protein folding. Amino acids are represented using five types of interaction sites (backbone alpha carbon; polar, apolar, positive and negative charges) for sidechain functional groups and capture essential steric and polarity information. Sidechain conformations can be predicted for a given fold to within 3 angstrom RMSD from the native structure.

  • RD Hills Jr, L Lu and GA Voth. 2010. Multiscale coarse-graining of the protein energy landscape. PLoS Comput. Biol. 6, e1000827. Open Access