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Alchembed: A Computational Method for Incorporating Multiple Proteins into Complex Lipid Geometries.

ABSTRACT: A necessary step prior to starting any membrane protein computer simulation is the creation of a well-packed configuration of protein(s) and lipids. Here, we demonstrate a method, alchembed, that can simultaneously and rapidly embed multiple proteins into arrangements of lipids described using either atomistic or coarse-grained force fields. During a short simulation, the interactions between the protein(s) and lipids are gradually switched on using a soft-core van der Waals potential. We validate the method on a range of membrane proteins and determine the optimal soft-core parameters required to insert membrane proteins. Since all of the major biomolecular codes include soft-core van der Waals potentials, no additional code is required to apply this method. A tutorial is included in the Supporting Information.

SUBMITTER: Jefferys E

PROVIDER: S-EPMC4467903 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Alchembed: A Computational Method for Incorporating Multiple Proteins into Complex Lipid Geometries.

Jefferys Elizabeth E Sands Zara A ZA Shi Jiye J Sansom Mark S P MS Fowler Philip W PW

Journal of chemical theory and computation 20150514 6

A necessary step prior to starting any membrane protein computer simulation is the creation of a well-packed configuration of protein(s) and lipids. Here, we demonstrate a method, <i>alchembed</i>, that can simultaneously and rapidly embed multiple proteins into arrangements of lipids described using either atomistic or coarse-grained force fields. During a short simulation, the interactions between the protein(s) and lipids are gradually switched on using a soft-core van der Waals potential. We ...[more]

PMID: 26089745

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Project description:BACKGROUND: With increasing numbers of crystal structures of proteinratioDNA and proteinratioproteinratioDNA complexes publically available, it is now possible to extract sufficient structural, physical-chemical and thermodynamic parameters to make general observations and predictions about their interactions. In particular, the properties of macromolecular assemblies of multiple proteins bound to DNA have not previously been investigated in detail. METHODOLOGY/PRINCIPAL FINDINGS: We have performed computational structural analyses on macromolecular assemblies of multiple proteins bound to DNA using a variety of different computational tools: PISA; PROMOTIF; X3DNA; ReadOut; DDNA and DCOMPLEX. Additionally, we have developed and employed an algorithm for approximate collision detection and overlapping volume estimation of two macromolecules. An implementation of this algorithm is available at http://promoterplot.fmi.ch/Collision1/. The results obtained are compared with structural, physical-chemical and thermodynamic parameters from proteinratioprotein and single proteinratioDNA complexes. Many of interface properties of multiple proteinratioDNA complexes were found to be very similar to those observed in binary proteinratioDNA and proteinratioprotein complexes. However, the conformational change of the DNA upon protein binding is significantly higher when multiple proteins bind to it than is observed when single proteins bind. The water mediated contacts are less important (found in less quantity) between the interfaces of components in ternary (proteinratioproteinratioDNA) complexes than in those of binary complexes (proteinratioprotein and proteinratioDNA).The thermodynamic stability of ternary complexes is also higher than in the binary interactions. Greater specificity and affinity of multiple proteins binding to DNA in comparison with binary protein-DNA interactions were observed. However, protein-protein binding affinities are stronger in complexes without the presence of DNA. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the interface properties: interface area; number of interface residues/atoms and hydrogen bonds; and the distribution of interface residues, hydrogen bonds, van der Walls contacts and secondary structure motifs are independent of whether or not a protein is in a binary or ternary complex with DNA. However, changes in the shape of the DNA reduce the off-rate of the proteins which greatly enhances the stability and specificity of ternary complexes compared to binary ones.

Dataset Information

Alchembed: A Computational Method for Incorporating Multiple Proteins into Complex Lipid Geometries.

Publications

Alchembed: A Computational Method for Incorporating Multiple Proteins into Complex Lipid Geometries.

Similar Datasets

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