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Increasing affinity of interferon-? receptor 1 to interferon-? by computer-aided design.

ABSTRACT: We describe a computer-based protocol to design protein mutations increasing binding affinity between ligand and its receptor. The method was applied to mutate interferon-? receptor 1 (IFN-?-Rx) to increase its affinity to natural ligand IFN-?, protein important for innate immunity. We analyzed all four available crystal structures of the IFN-?-Rx/IFN-? complex to identify 40 receptor residues forming the interface with IFN-?. For these 40 residues, we performed computational mutation analysis by substituting each of the interface receptor residues by the remaining standard amino acids. The corresponding changes of the free energy were calculated by a protocol consisting of FoldX and molecular dynamics calculations. Based on the computed changes of the free energy and on sequence conservation criteria obtained by the analysis of 32 receptor sequences from 19 different species, we selected 14 receptor variants predicted to increase the receptor affinity to IFN-?. These variants were expressed as recombinant proteins in Escherichia coli, and their affinities to IFN-? were determined experimentally by surface plasmon resonance (SPR). The SPR measurements showed that the simple computational protocol succeeded in finding two receptor variants with affinity to IFN-? increased about fivefold compared to the wild-type receptor.

SUBMITTER: Mikulecky P

PROVIDER: S-EPMC3807708 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Increasing affinity of interferon-γ receptor 1 to interferon-γ by computer-aided design.

Mikulecký Pavel P Cerný Jiří J Biedermannová Lada L Petroková Hana H Kuchař Milan M Vondrášek Jiří J Malý Petr P Šebo Peter P Schneider Bohdan B

BioMed research international 20131002

We describe a computer-based protocol to design protein mutations increasing binding affinity between ligand and its receptor. The method was applied to mutate interferon-γ receptor 1 (IFN-γ-Rx) to increase its affinity to natural ligand IFN-γ, protein important for innate immunity. We analyzed all four available crystal structures of the IFN-γ-Rx/IFN-γ complex to identify 40 receptor residues forming the interface with IFN-γ. For these 40 residues, we performed computational mutation analysis b ...[more]

PMID: 24199198

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Project description:Recent data indicates limited awareness and compliance on infection prevention procedures by dental offices and by dental laboratories. Guidelines for infection prevention in dentistry have been published by Centres for Disease Control and Prevention since 2003; the section "IX-Special consideration" includes a subsection concerning the prevention in dental laboratories, but it has not been modernised in later versions to fit the needs of traditional and computer-aided technology. Traditional techniques required disinfecting items (impression, chewing waxes, and appliances) with well-suited products, which are also chosen for limiting impression changes or appliance deterioration. Effective procedures are available with difficulties. Some of these contain irritant or non-eco-friendly disinfectants. The transport of impression, to dental laboratories, is often delayed with limited precautions for limiting cross-infection. Gypsum casts are frequently contaminated mainly by bacteria and their antibiotic-resistant strains and even stored for long periods during dental implant supported restoration and orthodontic therapy, becoming a hidden source of infection. Nowadays, computer-aided design/computer-aided manufacturing technology seems to be an interesting way to promote both business and safety, being more comfortable for patients and more accurate than traditional technology. A further advantage is easier infection prevention since, for the most part, mainly digital impression and casts are not a source of cross-infection and the transport of contaminated items is reduced and limited to try-in stages. Nevertheless, a peculiar feature is that a digital electronic file is of course unalterable, but may be ruined by a computer virus. Additionally, the reconditioning of scanner tips is determinant for the optical characteristics and long term use of the scanner, but information for its reconditioning from producers is often limited. This study focuses on some critical points including (a) insufficient guidelines, (b) choice of proper procedure for scanner reconditioning, and (c) data protection in relation to patient privacy.

Dataset Information

Increasing affinity of interferon-? receptor 1 to interferon-? by computer-aided design.

Publications

Increasing affinity of interferon-γ receptor 1 to interferon-γ by computer-aided design.

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