Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins

May, Ali; Pool, René; Dijk, Erik van; Bijlard, Jochem; Abeln, Sanne; Heringa, Jaap; Feenstra, K. Anton

doi:10.1093/bioinformatics/btt675

Cited by 41 publications

(38 citation statements)

References 51 publications

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“…491 Interestingly, it was also reported that coarsegrained models can accurately reproduce interaction strength for protein complexes of known structure. 492 An interesting example of a coarse-grained approach to protein docking is the ATTRACT model. 371 Starting from 2003, the ATTRACT model has been systematically improved and evolved in several docking applications.…”

Section: Protein Interactionsmentioning

confidence: 99%

Coarse-Grained Protein Models and Their Applications

et al. 2016

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The traditional computational modeling of protein structure, dynamics, and interactions remains difficult for many protein systems. It is mostly due to the size of protein conformational spaces and required simulation time scales that are still too large to be studied in atomistic detail. Lowering the level of protein representation from all-atom to coarse-grained opens up new possibilities for studying protein systems. In this review we provide an overview of coarse-grained models focusing on their design, including choices of representation, models of energy functions, sampling of conformational space, and applications in the modeling of protein structure, dynamics, and interactions. A more detailed description is given for applications of coarse-grained models suitable for efficient combinations with all-atom simulations in multiscale modeling strategies.

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Section: Protein Interactionsmentioning

confidence: 99%

Coarse-Grained Protein Models and Their Applications

et al. 2016

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“…To examine the contribution of the Ile‐Leu zipper interaction in the assemblies of TM helices of wSLN (wild‐typed SLN) and mSLNs (mutated SLNs), the multiple‐scaled MD including both atomistic (AT) and the coarse‐grained (CG) models were used. CG‐MD has been successfully applied in studying of the association of TM protein helix dimerization and the change of free energy, while the AT‐MD simulation could provide more structural details of dimer than the CG‐MD. Although the free energy given by CG models were larger than that by the AT model, a tendency to form dimer have been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Self‐assembling study of sarcolipin and its mutants in multiple molecular dynamic simulations

Cao

Wang

et al. 2017

Proteins

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The Sarcolipin (SLN) is a single trans-membrane protein that can self-assembly to dimer and oligomer for playing importantphysiological function. In this work, we addressed the dimerization of wild type SLN (wSLN) and its mutants (mSLNs) - I17A and I20A, using both coarse-grained (CG) and atomistic (AT) molecular dynamics (MD) simulations. Our results demonstrated that wSLN homodimer assembled as a left-handed helical complex, while mSLNs heterodimers assembled as right-handed complexes. Analysis of residue-residue contacts map indicated that isoleucine (Ile)-leucione (Leu) zipper domain played an important role in dimerization. The potential of mean force (PMF) demonstrated that wSLN homodimer was more stable than mSLNs heterodimers. Meanwhile, the mSLNs heterodimers preferred right-handed rather than left-handed helix. AT-MD simulations for wSLN and mSLNs were also in line with CG-MD simulations. These results provided the insights for understanding the mechanisms of SLNs self-assembling. Proteins 2017; 85:1065-1077. © 2017 Wiley Periodicals, Inc.

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“…They obtained a binding free energy of 12 kJ/mol between the peptide and the MHC class I molecule, which deviates considerably from the 32.2 kJ/mol binding free energy obtained from experiments . On the other hand, May et al applied WHAM with MARTINI CG force field to estimate the binding free energy between the peptide‐MHC‐Class‐I molecule and the T cell receptor (TCR) (PDB ID: 1AO7) and obtained a binding free energy of 80 kJ/mol, which compares well to the value of 78.6 kJ/mol obtained from experiments . To our knowledge, however, there is no reported study that has accurately estimated the binding free energy between a peptide and a MHC class II molecule.…”

Section: Introductionmentioning

confidence: 85%

Efficient estimation of binding free energies between peptides and an MHC class II molecule using coarse‐grained molecular dynamics simulations with a weighted histogram analysis method

Huang

Wen

et al. 2017

J Comput Chem

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We estimate the binding free energy between peptides and an MHC class II molecule using molecular dynamics (MD) simulations with the weighted histogram analysis method (WHAM). We show that, owing to its more thorough sampling in the available computational time, the binding free energy obtained by pulling the whole peptide using a coarse-grained (CG) force field (MARTINI) is less prone to significant error induced by inadequate-sampling than using an atomistic force field (AMBER). We further demonstrate that using CG MD to pull 3-4 residue peptide segments while leaving the remaining peptide segments in the binding groove and adding up the binding free energies of all peptide segments gives robust binding free energy estimations, which are in good agreement with the experimentally measured binding affinities for the peptide sequences studied. Our approach thus provides a promising and computationally efficient way to rapidly and reliably estimate the binding free energy between an arbitrary peptide and an MHC class II molecule. © 2017 Wiley Periodicals, Inc.

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Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins

Abstract: The python analysis framework and data files are available for download at http://www.ibi.vu.nl/downloads/bioinformatics-2013-btt675.tgz.

Cited by 41 publications

References 51 publications

Coarse-Grained Protein Models and Their Applications

Coarse-Grained Protein Models and Their Applications

Self‐assembling study of sarcolipin and its mutants in multiple molecular dynamic simulations

Efficient estimation of binding free energies between peptides and an MHC class II molecule using coarse‐grained molecular dynamics simulations with a weighted histogram analysis method

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