DStabilize: A Web Resource to Generate Mirror Images of Biomolecules.

Peptides comprising D-amino acids have been shown to be resistant to proteolysis. This makes them potential candidates as probes of cellular interactions, notably protein-biomolecule interactions. However, the empirical conversion of the amino acids that constitute a peptide from L-forms to D-forms will result in abrogation of the normal interactions made by the L-amino acids due to side-chain orientation changes that are associated with the changes in chirality. These interactions can be preserved by reversing the sequence of the D-peptide. We present a web server (http://dstabilize.bii.a-star.edu.sg/) that allows users to convert between L-proteins and D-proteins and for sequence reversal of D-peptides, along with the capability of performing other empirical geometric transforms. This resource allows the user to generate structures of interest easily for subsequent in silico processing.

[1]  S. Sidhu,et al.  A Potent d-Protein Antagonist of VEGF-A is Nonimmunogenic, Metabolically Stable, and Longer-Circulating in Vivo. , 2016, ACS chemical biology.

[2]  T. Maeda,et al.  Distribution of freed-serine in vertebrate brains , 1994, Brain Research.

[3]  Shosuke Kojo,et al.  Origin of Homochirality of Amino Acids in the Biosphere , 2010, Symmetry.

[4]  D. Lane,et al.  Macrocyclization of an all-d linear α-helical peptide imparts cellular permeability† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c9sc06383h , 2020, Chemical science.

[5]  Conrad C. Huang,et al.  UCSF Chimera—A visualization system for exploratory research and analysis , 2004, J. Comput. Chem..

[6]  Kumardeep Chaudhary,et al.  PEPstrMOD: structure prediction of peptides containing natural, non-natural and modified residues , 2015, Biology Direct.

[7]  Noriko Fujii,et al.  D-Amino Acids in Living Higher Organisms , 2002, Origins of life and evolution of the biosphere.

[8]  P. Kaumaya,et al.  Combination Treatment with HER-2 and VEGF Peptide Mimics Induces Potent Anti-tumor and Anti-angiogenic Responses in Vitro and in Vivo* , 2011, The Journal of Biological Chemistry.

[9]  W. Delano The PyMOL Molecular Graphics System , 2002 .

[10]  Olivier Michielin,et al.  SwissSidechain: a molecular and structural database of non-natural sidechains , 2012, Nucleic Acids Res..

[11]  Y. Kiriyama,et al.  D-Amino Acids in the Nervous and Endocrine Systems , 2016, Scientifica.

[12]  A. Hashimoto,et al.  Free d-aspartate and d-serine in the mammalian brain and periphery , 1997, Progress in Neurobiology.

[13]  Philip M. Kim,et al.  Method to generate highly stable D-amino acid analogs of bioactive helical peptides using a mirror image of the entire PDB , 2018, Proceedings of the National Academy of Sciences.

[14]  Bartek Wilczynski,et al.  Biopython: freely available Python tools for computational molecular biology and bioinformatics , 2009, Bioinform..

[15]  F. Cava,et al.  New Insights Into the Mechanisms and Biological Roles of D-Amino Acids in Complex Eco-Systems , 2018, Front. Microbiol..

[16]  Andreas Prlic,et al.  NGL viewer: web‐based molecular graphics for large complexes , 2018, Bioinform..

[17]  Chong Li,et al.  D-peptide inhibitors of the p53–MDM2 interaction for targeted molecular therapy of malignant neoplasms , 2010, Proceedings of the National Academy of Sciences.

[18]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[19]  G. Lu,et al.  The crystal structure of bar-headed goose hemoglobin in deoxy form: the allosteric mechanism of a hemoglobin species with high oxygen affinity. , 2001, Journal of molecular biology.

[20]  James M. Hogle,et al.  Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization , 2000, J. Comput. Aided Mol. Des..