Dataset Information

Efficient computation of transfer free energies of amino acids in beta-barrel membrane proteins.

ABSTRACT:

Motivation

Transmembrane beta-barrel proteins (TMBs) serve a multitude of essential cellular functions in Gram-negative bacteria, mitochondria and chloroplasts. Transfer free energies (TFEs) of residues in the transmembrane (TM) region provides fundamental quantifications of thermodynamic stabilities of TMBs, which are important for the folding and the membrane insertion processes, and may help in understanding the structure-function relationship. However, experimental measurement of TFEs of TMBs is challenging. Although a recent computational method can be used to calculate TFEs, the results of which are in excellent agreement with experimentally measured values, this method does not scale up, and is limited to small TMBs.

Results

We have developed an approximation method that calculates TFEs of TM residues in TMBs accurately, with which depth-dependent transfer free energy profiles can be derived. Our results are in excellent agreement with experimental measurements. This method is efficient and applicable to all bacterial TMBs regardless of the size of the protein.

Availability and implementation

An online webserver is available at http://tanto.bioe.uic.edu/tmb-tfe .

Contact

: jliang@uic.edu.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Tian W

PROVIDER: S-EPMC5860226 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Efficient computation of transfer free energies of amino acids in beta-barrel membrane proteins.

Tian Wei W Lin Meishan M Naveed Hammad H Liang Jie J

Bioinformatics (Oxford, England) 20170601 11

<h4>Motivation</h4>Transmembrane beta-barrel proteins (TMBs) serve a multitude of essential cellular functions in Gram-negative bacteria, mitochondria and chloroplasts. Transfer free energies (TFEs) of residues in the transmembrane (TM) region provides fundamental quantifications of thermodynamic stabilities of TMBs, which are important for the folding and the membrane insertion processes, and may help in understanding the structure-function relationship. However, experimental measurement of TFE ...[more]

PMID: 28158457

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Project description:The effects of macromolecular crowding on the thermodynamic properties of test proteins are determined by the latter's transfer free energies from a dilute solution to a crowded solution. The transfer free energies in turn are determined by effective protein-crowder interactions. When these interactions are modeled at the all-atom level, the transfer free energies may defy simple predictions. Here we investigated the dependence of the transfer free energy (Δμ) on crowder concentration. We represented both the test protein and the crowder proteins atomistically, and used a general interaction potential consisting of hard-core repulsion, non-polar attraction, and solvent-screened electrostatic terms. The chemical potential was rigorously calculated by FMAP (Qin and Zhou, 2014), which entails expressing the protein-crowder interaction terms as correlation functions and evaluating them via fast Fourier transform (FFT). To high accuracy, the transfer free energy can be decomposed into an excluded-volume component (Δμe-v), arising from the hard-core repulsion, and a soft-attraction component (Δμs-a), arising from non-polar and electrostatic interactions. The decomposition provides physical insight into crowding effects, in particular why such effects are very modest on protein folding stability. Further decomposition of Δμs-a into non-polar and electrostatic components does not work, because these two types of interactions are highly correlated in contributing to Δμs-a. We found that Δμe-v fits well to the generalized fundamental measure theory (Qin and Zhou, 2010), which accounts for atomic details of the test protein but approximates the crowder proteins as spherical particles. Most interestingly, Δμs-a has a nearly linear dependence on crowder concentration. The latter result can be understood within a perturbed virial expansion of Δμ (in powers of crowder concentration), with Δμe-v as reference. Whereas the second virial coefficient deviates strongly from that of the reference system, higher virial coefficients are close to their reference counterparts, thus leaving the linear term to make the dominant contribution to Δμs-a.

Dataset Information

Efficient computation of transfer free energies of amino acids in beta-barrel membrane proteins.

Motivation

Results

Availability and implementation

Contact

Supplementary information

Publications

Efficient computation of transfer free energies of amino acids in beta-barrel membrane proteins.

Similar Datasets

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