Beyond Supersecondary Structure: Physics-Based Sequence Alignment.

Traditional approaches to sequence alignment are based on evolutionary ideas. As a result, they are prebiased toward results which are in accord with initial expectations. We present here a method of sequence alignment which is based entirely on the physical properties of the amino acids. This approach has no inherent bias, eliminates much of the computational complexity associated with methods currently in use, and has been shown to give good results for structures which were poorly predicted by traditional methods in recent CASP competitions and to identify sequence differences which correlate with structural and dynamic differences not detectable by traditional methods.

[1]  S. Rackovsky.  Nonlinearities in protein space limit the utility of informatics in protein biophysics , 2015, Proteins.

[2]  S. Rackovsky,et al.  Alternative approach to protein structure prediction based on sequential similarity of physical properties , 2015, Proceedings of the National Academy of Sciences.

[3]  S Rackovsky,et al.  "Hidden" sequence periodicities and protein architecture. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  S. Rackovsky.  Sequence determinants of protein architecture , 2013, Proteins.

[5]  H. Scheraga,et al.  Prediction of structural homology between bovine -lactalbumin and hen egg white lysozyme. , 1971, Archives of biochemistry and biophysics.

[6]  Douglas L. Brutlag,et al.  Remote homology detection: a motif based approach , 2003, ISMB.

[7]  S. Rackovsky.  Spectral analysis of a protein conformational switch. , 2011, Physical review letters.

[8]  P K Warme,et al.  Computation of structures of homologous proteins. Alpha-lactalbumin from lysozyme. , 1974, Biochemistry.

[9]  S Rackovsky,et al.  Sequence-, structure-, and dynamics-based comparisons of structurally homologous CheY-like proteins , 2017, Proceedings of the National Academy of Sciences.

[10]  Akinori Kidera,et al.  Relation between sequence similarity and structural similarity in proteins. Role of important properties of amino acids , 1985 .

[12]  Rajender S. Sangwan,et al.  Fundamentals of Homology Modeling Steps and Comparison among Important Bioinformatics Tools: An Overview , 2013 .

[13]  P. Alexander,et al.  A minimal sequence code for switching protein structure and function , 2009, Proceedings of the National Academy of Sciences.

[14]  H. Scheraga,et al.  Statistical analysis of the physical properties of the 20 naturally occurring amino acids , 1985 .

[15]  S. Rackovsky.  Sequence physical properties encode the global organization of protein structure space , 2009, Proceedings of the National Academy of Sciences.