Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
+44 1223 790975
ISSN: 0974-276X
+44 1223 790975
Emmanuelle Bignon
Danish Cancer Society, Denmark
Scientific Tracks Abstracts: J Proteomics Bioinform
Nitric oxide plays an important role in the redox signaling pathway. Indeed, its reaction with cysteines, resulting in the formation of S-nitrosothiols, has shown to be involved in a broad variety of biochemical and physiological processes in a large variety of organisms. Large amounts of investigations have been led in order to understand the regulation mechanisms driven by protein S-nitrosylation and their implications in cancer cells development. Thousands of proteins have been proven to undergo S-nitrosylation in vivo and the dysregulation of this process is implicated in various types of severe diseases, including cancer onset, progression and treatment resistance. Thus, the understanding of S- nitrosylated proteins (SNOproteins) structural behavior and reactivity is of utmost importance towards the development of new anti-cancer therapeutics. Nowadays, there is a lack of information concerning the structural and electronic features of nitrosylated cysteine, with only few NMR and x-ray structures reported for SNO proteins. In this framework, molecular modeling has been proven to be a useful tool to obtain predictive structural and dynamical behavior of biomolecules. The S-nitrosocysteine (CysNO) non-canonical amino acid exhibits a very complex chemistry, due to the presence of two antagonist resonance structures with very different electronic features. Therefore, the accurate description of this moiety��?s structure is highly challenging, and prediction of its chemical properties has to be performed using high-level quantum methods. Unfortunately, such methods are strongly timeconsuming, and their computational cost is prohibitive for the study of large system such as proteins. Force field parameters have been developed in order to perform classical molecular dynamics simulations of S-nitrosylated proteins to decipher their dynamical features. Nevertheless, the accuracy of these parameters has not been extensively cross-validated and still need to be tested. For this purpose, we performed extensive all-atom classical molecular dynamics simulations on proteins for which the crystal structures harboring CysNO have been reported. The conformations sampled by all atom simulations with the two sets of parameters have been confronted to the experimental structures in order to validate their efficiency in reproducing CysNO behavior. This checking is an important step in the design of accurate force field parameters, which would allow computational chemist to investigate the dynamical properties of S-nitrosylated proteins and their involvement in cancer cells mechanisms. Recent Publications 1. Hess D T, Matsumoto A, Kim S O, Marshall H E and Stamler J S (2005) Protein S-nitrosylation: purview and parameters. Nature Reviews Molecular Cell Biology 6(2):150. 2. Wang, Z (2012) Protein S-nitrosylation and cancer. Cancer Letters 320(2):123-129. 3. Karplus M and McCammon J A (2002) Molecular dynamics simulations of biomolecules. Nature Structural and Molecular Biology 9(9):646. 4. Han S (2008) Force field parameters for S-nitrosocysteine and molecular dynamics simulations of S-nitrosated thioredoxin. Biochemical and Biophysical Research Communications 377(2):612-616. 5. Petrov D, Margreitter C, Grandits M, Oostenbrink C and Zagrovic B (2013) A systematic framework for molecular dynamics simulations of protein post-translational modifications. PLoS computational biology 9(7):e1003154.