CHARMM-GUI Input Generator for NAMD, Gromacs, Amber, Openmm, and CHARMM/OpenMM Simulations using the CHARMM36 Additive Force Field

Lee, Jumin; Cheng, Xi; Jo, Sunhwan; MacKerell, Alexander D.; Klauda, Jeffery B.; Im, Wonpil

doi:10.1016/j.bpj.2015.11.3431

Cited by 397 publications

(417 citation statements)

References 0 publications

Supporting

Mentioning

413

Contrasting

Order By: Relevance

“…A total of 50 loop models were generated, and the structure with the top discrete optimized protein energy (DOPE) 46 score was selected as an initial conformation for the loop. The starting system for MD simulations was assembled with the Membrane Builder functionality of the CHARMM-GUI webserver 47,48 . This system (box dimension: 143 Å × 143 Å × 147 Å) consisted of the TRPV5 tetramer, ( R )- or ( S )-econazole molecules bound to each tetramer subunit, 450 POPC molecules, 58,725–59,185 water molecules, 213–215 sodium ions, 183–185 chloride ions, and a calcium ion in the outer pore region, totaling 276,224 atoms in the case of TRPV5 bound to ( R )-econazole and 277,608 atoms for TRPV5 bound to ( S )-econazole.…”

Section: Methodsmentioning

confidence: 99%

Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM

Hughes

Lodowski

Huynh

et al. 2018

Nat Struct Mol Biol

116

143

View full text Add to dashboard Cite

The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca2+, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca2+ reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels. The econazole-bound TRPV5 structure adopts a closed conformation with a distinct lower gate that occludes Ca2+ permeation through the channel. Structural comparisons between TRPV5 and other TRPV channels, complemented with molecular dynamics (MD) simulations of the econazole-bound TRPV5 structure, allowed us to gain mechanistic insight into TRPV5 channel inhibition by small molecules.

show abstract

Section: Methodsmentioning

confidence: 99%

Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM

Hughes

Lodowski

Huynh

et al. 2018

Nat Struct Mol Biol

116

143

View full text Add to dashboard Cite

show abstract

“…All atomistic simulations were carried out using the GROMACS MD engine. Atomistic parameters for the proteins, lipids, TIP3P, and ions were determined according to the CHARMM36 force field . For protein structure optimization, a single protein was embedded in a 1‐palmitoyl‐2‐oleoyl‐ sn ‐glycero‐3‐phosphocholine (POPC) lipid membrane.…”

Section: Methodsmentioning

confidence: 99%

“…The bonds with hydrogen atoms were constraints and were solved using the linear constraint solver (LINCS). Long‐range electrostatic interactions were calculated using the particle mesh Ewald (PME) algorithm at 1.2‐nm cutoff, and the van der Waal's interactions were calculated with 1.2‐nm cutoff …”

Section: Methodsmentioning

confidence: 99%

Architecture of the paracellular channels formed by claudins of the blood–brain barrier tight junctions

Irudayanathan

Wang

et al. 2017

Annals of the New York Academy of Sciences

119

View full text Add to dashboard Cite

Tight junctions (TJs) are key players in determining tissue-specific paracellular permeability across epithelial and endothelial membranes. Claudin proteins, the primary determinants of TJs structure and functionality, assemble in paracellular spaces to form channels and pores that are charge and size selective. Here, using molecular dynamics (MD) simulations, we elucidate the molecular assembly of claudin-3 and claudin-5 proteins of blood-brain barrier TJs. Despite having a high degree of sequence and structural similarity, these two claudins form different types of cis-interactions. Molecular docking of the observed cis-interfaces into trans-forms revealed two putative pore models that were also observed in the self-assembly simulations. The observed pore structures (pore I and II) have pore-lining residues that have been previously reported in the literature. The pore I model is consistent with a previously reported claudin-15 model. The pore II model, also consistent with biochemical results, has not been reported previously. Further analysis using in silico site-directed mutations provide convincing support for the validity of the pore II model. Using steered MD and umbrella sampling, we computed the transport properties of water and α-d-glucose through pore II. The study offers new insight into the selectivity of blood-brain barrier TJs.

show abstract

“…CHARMM-GUI Membrane Builder is widely used for system building in homogenous or mixed bilayers with more than 180 lipid types available [160,161]. It also provides well-validated equilibration and production inputs for many MD program packages (CHARMM, NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM) [162]. While it is difficult to estimate the correct number of lipids in each leaflet of protein–membrane systems to avoid a mismatch in lipid packing, it has been suggested that the area per lipid mismatch up to 5% would be tolerable in membrane simulations of typical all-atom system sizes [163].…”

Section: Molecular Models For Membranes and Membrane Proteinsmentioning

confidence: 99%

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms

Mori

Miyashita²,

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

Self Cite

116

108

View full text Add to dashboard Cite

This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins. Guest Editors: J.C. Gumbart and Sergei Noskov.

show abstract

CHARMM-GUI Input Generator for NAMD, Gromacs, Amber, Openmm, and CHARMM/OpenMM Simulations using the CHARMM36 Additive Force Field

Cited by 397 publications

References 0 publications

Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM

Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM

Architecture of the paracellular channels formed by claudins of the blood–brain barrier tight junctions

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms

Contact Info

Product

Resources

About