Technology used for computational drug design starts much earlier than at the protein structure. Below is a description:
- DNA sequence
- System biology analysis
- Target identification and discrimination (do not kill the host!)
- Target selection and model building
- Computational screening of molecules against a given target in a specific area.
- Selection of hits and improvement in silico
- Testing hits in a lab
- Selection of the improved hits
- Optimization for max potency and min toxicity
The technology is used for antibacterial and antifungal drug design.
Technology for vaccine design is very similar. A brief description is below:
- DNA sequence
- Systems biology
- Target selection
- Genetic engineering of the host for vaccine production
- Testing in animal model of infection
The described approach is being used to design vaccine against periodontosis caused by a bacterial pathogen. Project is funded by the National Science Center of Poland, grant OPUS 11, panel NZ6, awarded to Dr. Swietnicki.
Vaccine design is more complicated than simply decorating a carrier with surface proteins and structures of outside fragments. Many commercial companies can attest to it by commercial failures of their products based on that sole assumption.
A brief description what is required for each stage is given under Computational Laboratory. More details requires a commitment to initiating a project.
- Swietnicki, W., Goldeman, W., Psurski, M., Nasulewicz-Goldeman, A., Boguszewska-Czubara, A., Drab, M., Sycz, J., Goszczyński, T.M. Metallacarborane derivatives effective against Pseudomonas aeruginosa and Yersinia enterocolitica. MDPI International Journal of Molecular Sciences 2021, 22(13), 6762. https://www.mdpi.com/1422-0067/22/13/6762.
- Swietnicki, W. Secretory System Components as Potential Prophylactic Targets for
Bacterial Pathogens. Biomolecules 2021, 11(6), 892; doi.org/10.3390/biom11060892.
- Swietnicki, W; Caspi, R. Prediction of Selected Biosynthetic Pathways for the Lipopolysaccharide Components in Porphyromonas gingivalis. MDPI Pathogens 2021, 10(3), 374. doi.org/10.3390/pathogens10030374.
- Chatterjee, P.; Sass, G.; Swietnicki, W.; Stevens, D.A. Review of Potential Pseudomonas Weaponry, Relevant to the Pseudomonas–Aspergillus Interplay, for the Mycology Community. J. Fungi 2020, 6, 81. doi.org/10.3390/jof6020081.
- Swietnicki W, Brzozowska E. In silico analysis of bacteriophage tail tubular proteins suggests a putative sugar binding site and a catalytic mechanism, J Mol Graph Mod. 2019, 92: 8-16.
- Swietnicki W., Czarny A., Antkowiak L., Zaczynska E., Kolodziejczak M., Sycz J., Stachowicz L., Alicka M., Marycz K. Identification of a potent inhibitor of type II secretion system from Pseudomonas aeruginosa, Biochem Biophys Res Commun. 2019, https://doi.org/10.1016/j.bbrc.2019.04.055.
- Swietnicki W, Czarny A, Urbanska N, Drab M. Identification of small molecule compounds active against Staphylococcus aureus and Proteus mirabilis. Biochem Biophys Res Commun. 2018 Nov;506(4):1047-1051.
- Bzdzion L, Krezel H, Wrzeszcz K, Grzegorek I, Nowinska K, Chodaczek G, Swietnicki W. Design of small molecule inhibitors of type III secretion system ATPase EscN from enteropathogenic Escherichia coli. Acta Biochim Pol. 2017;64(1):49-63.
- Milczarek M, Filip-Psurska B, Swiętnicki W, Kutner A, Wietrzyk J. Vitamin D analogs combined with 5-fluorouracil in human HT-29 colon cancer treatment. Oncol Rep. 2014 Aug;32(2):491-504.
- Sambuughin N, Swietnicki W, Techtmann S, Matrosova V, Wallace T, Goldfarb L, Maynard E. KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase. Biochem Biophys Res Commun. 2012 May 18;421(4):743-749.
- Kong Q, Mills JL, Kundu B, Li X, Qing L, Surewicz K, Cali I, Huang S, Zheng M, Swietnicki W, Sönnichsen FD, Gambetti P, Surewicz WK. Thermodynamic stabilization of the folded domain of prion protein inhibits prion infection in vivo. Cell Rep. 2013 Jul 25;4(2):248-54.
- Bozue J, Cote CK, Webster W, Bassett A, Tobery S, Little S, Swietnicki W. A Yersinia pestis YscN ATPase mutant functions as a live attenuated vaccine against bubonic plague in mice. FEMS Microbiol Lett. 2012 Jul;332(2):113-21.
- Swietnicki W, Carmany D, Retford M, Guelta M, Dorsey R, Bozue J, Lee MS, Olson MA. Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase. PLoS One. 2011;6(5):e19716.
- Swietnicki W, Barnie AM, Dyas BK, Ulrich RG. Zinc binding and dimerization of Streptococcus pyogenes pyrogenic exotoxin C are not essential for T-cell stimulation. J Biol Chem. 2003 Mar 14;278(11):9885-95. Epub 2002 Dec 8.
Patents in the Polish Patent Office:
- PAT.226024: New application of N-[2-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]ethyl]-2-oxo-1,5,6,7-tetrahydrocyclopenta[b] pyridyno-3-carboxyamide
- Application# P.409676: New application of 2-(phenylsulfanyl)-acetamide derivatives, Patent application in progress.