Protein Structural Statistics with PSS

Characterizing the variability within an ensemble of protein structures is a common requirement in structural biology and bioinformatics. With the increasing number of protein structures becoming available, there is a need for new tools capable of automating the structural comparison of large ensemble of structures. We present Protein Structural Statistics (PSS), a command-line program written in Perl for Unix-like environments, dedicated to the calculation of structural statistics for a set of proteins. PSS can perform multiple sequence alignments, structure superpositions, calculate Cartesian and dihedral coordinate statistics, and execute cluster analyses. An HTML report that contains a convenient summary of results with figures, tables, and hyperlinks can also be produced. PSS is a new tool providing an automated way to compare multiple structures. It integrates various types of structural analyses through an user-friendly and flexible interface, facilitating the access to powerful but more specialized programs. PSS is easy to modify and extend and is distributed under a free and open source license. The relevance of PSS is illustrated by examples of application to pertinent biological problems.

[1]  Valentin A. Ilyin,et al.  Friend, an integrated analytical front-end application for bioinformatics , 2005, Bioinform..

[2]  C. Ottmann,et al.  Synthesis and Crystal Structure of a Phosphorylated Estrogen Receptor Ligand Binding Domain , 2010, Chembiochem : a European journal of chemical biology.

[3]  Narayanaswamy Srinivasan,et al.  iPBA: a tool for protein structure comparison using sequence alignment strategies , 2011, Nucleic Acids Res..

[4]  Chris Sander,et al.  Dali/FSSP classification of three-dimensional protein folds , 1997, Nucleic Acids Res..

[5]  A. Lesk,et al.  The relation between the divergence of sequence and structure in proteins. , 1986, The EMBO journal.

[6]  D. Moras,et al.  Phosphorylation by PKA potentiates retinoic acid receptor alpha activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  András Fiser,et al.  Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments , 2007, Bioinform..

[8]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[9]  Narayanan Eswar,et al.  Alignment of multiple protein structures based on sequence and structure features. , 2009, Protein engineering, design & selection : PEDS.

[10]  Kornelia Polyak,et al.  Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex , 1995, Nature.

[11]  Oliver Beckstein,et al.  MDAnalysis: A toolkit for the analysis of molecular dynamics simulations , 2011, J. Comput. Chem..

[12]  Vincent B. Chen,et al.  Correspondence e-mail: , 2000 .

[13]  Satoru Miyano,et al.  Open source clustering software , 2004 .

[14]  David S. Wishart,et al.  SuperPose: a simple server for sophisticated structural superposition , 2004, Nucleic Acids Res..

[15]  David O. Morgan,et al.  A novel cyclin associates with M015/CDK7 to form the CDK-activating kinase , 1994, Cell.

[16]  J. Newport,et al.  Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes , 1991, Cell.

[17]  P. Nurse,et al.  Animal cell cycles and their control. , 1992, Annual review of biochemistry.

[18]  Jianyin Shao,et al.  Clustering Molecular Dynamics Trajectories: 1. Characterizing the Performance of Different Clustering Algorithms. , 2007, Journal of chemical theory and computation.

[19]  A. Sali,et al.  Alignment of protein sequences by their profiles , 2004, Protein science : a publication of the Protein Society.

[20]  M. Karplus,et al.  Multiple Conformations of RGDW and dRGDW: A Theoretical Study and Comparison with NMR Results , 2000 .

[21]  J. Richardson,et al.  The penultimate rotamer library , 2000, Proteins.

[22]  Holger Gohlke,et al.  The Amber biomolecular simulation programs , 2005, J. Comput. Chem..

[23]  Olivier Poch,et al.  Signature of the oligomeric behaviour of nuclear receptors at the sequence and structural level , 2004, EMBO reports.

[24]  Sung-Hou Kim,et al.  Crystal structure of cyclin-dependent kinase 2 , 1993, Nature.

[25]  C. Brooks,et al.  Statistical clustering techniques for the analysis of long molecular dynamics trajectories: analysis of 2.2-ns trajectories of YPGDV. , 1993, Biochemistry.

[26]  R Pepperkok,et al.  Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts , 1993, The Journal of cell biology.

[27]  J. Skolnick,et al.  TM-align: a protein structure alignment algorithm based on the TM-score , 2005, Nucleic acids research.

[28]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[29]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[30]  Andrej Sali,et al.  Variable gap penalty for protein sequence-structure alignment. , 2006, Protein engineering, design & selection : PEDS.

[31]  A. Bilancio,et al.  Steroid‐induced androgen receptor–oestradiol receptor β–Src complex triggers prostate cancer cell proliferation , 2000, The EMBO journal.

[32]  Yanchun Yang,et al.  Markov model plus k-word distributions: a synergy that produces novel statistical measures for sequence comparison , 2008, Bioinform..

[33]  J. Thornton,et al.  AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR , 1996, Journal of biomolecular NMR.

[34]  Y. Duan,et al.  Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations , 2007, Proceedings of the National Academy of Sciences.

[35]  J. Pines,et al.  Cyclins and their associated cyclin-dependent kinases in the human cell cycle. , 1993, Biochemical Society transactions.

[36]  Jianpeng Ma,et al.  CHARMM: The biomolecular simulation program , 2009, J. Comput. Chem..

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

[38]  M. Barone,et al.  Tyrosine phosphorylation of estradiol receptor by Src regulates its hormone-dependent nuclear export and cell cycle progression in breast cancer cells , 2012, Oncogene.

[39]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[40]  G. Castoria,et al.  Sex-steroid hormones and EGF signalling in breast and prostate cancer cells: Targeting the association of Src with steroid receptors , 2008, Steroids.