Detection of Hydrophobic Clusters in Molecular Dynamics Protein Unfolding Simulations Using Association Rules

One way of exploring protein unfolding events associated with the development of Amyloid diseases is through the use of multiple Molecular Dynamics Protein Unfolding Simulations. The analysis of the huge amount of data generated in these simulations is not a trivial task. In the present report, we demonstrate the use of Association Rules applied to the analysis of the variation profiles of the Solvent Accessible Surface Area of the 127 amino-acid residues of the protein Transthyretin, along multiple simulations. This allowed us to identify a set of 28 hydrophobic residues forming a hydrophobic cluster that might be essential in the unfolding and folding processes of Transthyretin.

[1]  Werner Dubitzky,et al.  Protein folding and unfolding simulations: a new challenge for data mining. , 2004, Omics : a journal of integrative biology.

[2]  Ramakrishnan Srikant,et al.  Fast Algorithms for Mining Association Rules in Large Databases , 1994, VLDB.

[3]  David A C Beck,et al.  Methods for molecular dynamics simulations of protein folding/unfolding in solution. , 2004, Methods.

[4]  S M Breathnach,et al.  Amyloid and amyloidosis. , 1988, Journal of the American Academy of Dermatology.

[5]  Rui M. M. Brito,et al.  Tetramer Dissociation and Monomer Partial Unfolding Precedes Protofibril Formation in Amyloidogenic Transthyretin Variants* , 2001, The Journal of Biological Chemistry.

[6]  J. Hamilton,et al.  The X-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30→Met variant to 1.7-Å resolution , 1993 .

[7]  Alexander D. MacKerell,et al.  All-atom empirical potential for molecular modeling and dynamics studies of proteins. , 1998, The journal of physical chemistry. B.

[8]  Hal Malehorn.  A class project , 1977 .

[9]  Ramakrishnan Srikant,et al.  Fast algorithms for mining association rules , 1998, VLDB 1998.

[10]  J Rodrigues,et al.  How Important is the Role of Compact Denatured States on Amyloid Formation by Transthyretin , 2004 .

[11]  J. Hamilton,et al.  The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution. , 1993, The Journal of biological chemistry.

[12]  Paulo J. Azevedo.  CAREN - A java based apriori implementation for classification purposes , 2003 .

[13]  Rui M. M. Brito,et al.  Amyloid Formation by Transthyretin: From Protein Stability to Protein Aggregation , 2003 .

[14]  Jan Hermans,et al.  Hydrophilicity of cavities in proteins , 1996 .

[15]  Michael R. Shirts,et al.  Atomistic protein folding simulations on the submillisecond time scale using worldwide distributed computing. , 2003, Biopolymers.

[16]  Laxmikant V. Kale,et al.  NAMD2: Greater Scalability for Parallel Molecular Dynamics , 1999 .

[17]  V. Daggett.  Molecular dynamics simulations of the protein unfolding/folding reaction. , 2002, Accounts of chemical research.