Curriculum Vita                                                                                   Valentin A. Ilyin, PhD

 

Email: ilyinv@bc.edu

Address: Biology Department, Boston College, 140 Commonwealth Ave.Chestnut Hill, MA 02467

tel. (617) 552-3540, fax (617) 552-2011, valentin.ilyin@bc.edu

 

Education

1988, MS in Molecular Biology, Moscow Institute of Physics and Technology, MPTI (fiztech).

1992, PhD in Physics and Mathematics, Shubnikov Institute of Crystallography, Moscow. Boris Vainstein lab. Study and work on Protein Theory, Crystallography Theory and Experiment, PhD in Physics and Mathematics, area: Solid State Physics, specialization in Protein Crystallography 1992.

 

Experience in Protein Crystallography/Computational Structural Biology:

 

11/1991 - 2/1995, Scientist, Group Leader, Boris Vainstein lab, Institute of Crystallography, Moscow, Russia. Work included several scientific projects on protein structure analysis and development computational tools for protein analysis. Work on Refinement methods, protein solvent accessibility, and crystal structures for DD-carboxipeptidase and Extracellular guanyl-specific RNAase of the fungus Aspergillus pallidus (RNAase ApI).

 

2/1999 - 5/1999, Programming Researcher, Cold Spring Harbor Laboratory, NY.

Short-term project on development tools for protein sequence/structure analysis.

 

1/1995 - 1/2000, Postdoctoral Fellow, Research Associate, Charles Carter lab, University of North Carolina at Chapel Hill, NC. Protein Crystallography, participated in development and implementations on Maximum Entropy and Bayesian statistics and application to Refinement of Protein Structures (solvent flattering), methods of non-crystallography symmetry for refinement, X-ray structure of Tryptophanyl-tRNA synthetase and several enzyme/substrate complexes. Refinement methods for Biomolecular Crystallography.

 

Experience in Computational Biology/Bioinformatics/Biostatistics:

 

2/2000 – 7/2002, Research Associate, Andrej Sali lab, Rockefeller University, NY.

Participated in development of homology modeling software, MODELLER, database of comparative structure models, MODBASE, pipeline of large-scale structural genomics (>500,000 protein models), MODPIPE, target selection for Structural Genomics, front-end analytical and visualization tools and database interface to multiple sequence structure resources, ModView, Bioinformatics Databases: Ligand database, LigBase, Structural alignments database, DBAli.

 

7/2002 – 6/2009, Assistant Professor of Bioinformatics, Northeastern University, Boston, MA. Please see the publication list, bioinformatics software and research projects descriptions below.

 

7/2009 – current, Research Associate Professor, Biology Department, Boston College, Chestnut Hill, MA

 


Publications[1] available at our web site: http://ilyinlab.org/public/refs.html

 

8 protein structures in PDB: 1d2r, 1fi4, 1i9a, 1jr7, 1m83, 1mau, 1maw, 1mb2.

 

Presentations

 

Since 2002 our projects have been presented at over 45 posters at national and international meetings.

 

Invited Talks

V. Ilyin, “An accurate structural alignment by TOPOFIT”, Broad Institute, MIT, on Apr 28, 2009

A. Abyzov, A. Uzun, P.Strauss, and V. Ilyin, "AP endonuclease 1- DNA polymerase beta: Theoretical prediction of interacting surfaces", Mar 17, 2008, MIT's Boston DNA Repair and Mutagenesis (DRAM) Group, MIT, Cambridge, MA

V. Ilyin, "Widespread occurrence of non-sequential relations among proteins detected by TOPOFIT. Do proteins evolve as we think they do?"  November 20, 2007, University of Chicago & Argonne National Lab, Chicago.

V. Ilyin, Non-sequential alignments in protein structure comparison: rare exceptions or protein feature? Northeastern University, on Sep 19, 2007

V. Ilyin, “An accurate structural alignment by TOPOFIT”, Boston University, on Mar 28, 2006. 

V. Ilyin, "Friend, an Integrated Front-End Application for Bioinformatics", Clark University, Worcester, on Apr 27, 2004.

V. Ilyin, Mapping sequence features on protein structure and vise versa. Second Northeast Bioinformatics Consortium Conference October 24-25, 2003, Boston, MA.

V. Ilyin, Applying Bioinformatics for Molecular Modeling, Oct 20, 2003, Talk at Bouve College, Northeastern University

V. Ilyin, Bioinformatics Methods, Feb 28, 2003, Computer Science College, Boston

V. Ilyin, Non-Polar Nuclei in Proteins and Front-End Applications for Bioinformatics, Virginia Tech University, May 12, 2002

V. Ilyin, Non-Polar Nuclei in Proteins and Front-End Applications for Bioinformatics, Koln University, Germany, Apr 17, 2002

 

 

 

Funding

 

National Institute of Health, National Library of Medicine, RO1, Accurate protein structural comparisons by TOPOFIT. 1R01LM009519-01A1

PI: Valentin Ilyin, $714,600, 2008-2011.

The goal of the project is to employ the advantages and new opportunities provided by the TOPOFIT approach to the systematic analysis of protein structures in general, and together with many other emerging methods to apply specific biological problems toward developing a new insight into protein stability, functionality, specificity and evolution, and to facilitate the development of new therapeutics to cure diseases.

 

ICSS (Institute of Complex Scientific Software), $24,000, Valentin Ilyin as co-PI, together with Computer and Engineering Dept.)

         Integration of metabolic pathways and diseases information into our StructureSNP web server to address specific biomedical problems.

 

Public web-based Bioinformatics resources developed

 

Main public web site: http://ilyinlab.org

 

Friend, an Integrated Analytical Front-End Application for Bioinformatics

Friend is a bioinformatics application designed for simultaneous analysis and visualization of multiple structures and sequences of proteins and/or DNA/RNA. The application provides extended functionalities such as: structure visualization with different rendering and coloring, sequence alignment, and simple phylogeny analysis, along with a number of advanced features to perform more complex analyses of sequence structure relationships, including: structural alignment of proteins, investigation of specific interaction motifs, studies of protein-protein, protein-DNA, and protein-ligand interactions in protein super-families. Friend is also useful for the functional annotation of proteins, target identification, protein modeling, and protein folding studies. Friend provides three levels of usage; 1) an extensive GUI for a scientist with no programming experience, 2) a command line interface for scripting for a scientist with some programming experience, and 3) the ability to extend Friend with user written libraries for an experienced programmer. The application is linked and communicates with local and remote sequence and structure databases. Friend is also now available in Applet form, which empowers users with all the functionality currently found in Friend, and provides a new web-based presentation platform, with detailed organization and manipulation of structure/sequence information, at the press of a button. Friend is a popular Bioinformatics application, with > 100 downloads per month since 2005. We are constantly upgrading the Friend software package with new functionality. http://ilyinlab.org/friend

 

        

TOPOFIT-DB, a database of protein structure alignment based on our TOPOFIT method.

 

TOPOFIT-DB (T-DB) is a structure database of structural relations between all protein. Currently T-DB has some specific aims: 1). First to help researchers locate and analyze the structure neighbors found by the TOPOFIT method; including functional amino acids conservation, structural core analysis, and flexible region analysis. 2). Secondly, to give researchers, such as crystallographers, a portal through which one-to-all comparison of a newly determined structure against the entire PDB can be carried out. 3). Finally, through its online visualization software (Friend), provide users with the ability to quickly analyze the structural alignments stored in T-DB. http://ilyinlab.org/topofit

 

*) The new T-DB 2009 with all the up-to-date structural relations has already been calculated and we are in process of finalizing and releasing the update.

 

StSNP, Structural non-synonymous SNPs (single nucleotide polymorphism) web server

SNPs located within the open reading frame of a gene that result in an alteration in the amino acid sequence of the encoded protein [nonsynonymous SNPs (nsSNPs)] might directly or indirectly affect functionality of the protein, alone or in the interactions in a multi-protein complex, by increasing/decreasing the activity of the metabolic pathway. Understanding the functional consequences of such changes and drawing conclusions about the molecular basis of diseases, involves integrating information from multiple heterogeneous sources including sequence, structure data and pathway relations between proteins. The data from NCBI's SNP database (dbSNP), gene and protein databases from Entrez, protein structures from the PDB and pathway information from KEGG have all been cross referenced into the StSNP web server, in an effort to provide combined integrated, reports about nsSNPs. StSNP provides 'on the fly' comparative modeling of nsSNPs with links to metabolic pathway information, along with real-time visual comparative analysis of the modeled structures using the Friend software application. The use of metabolic pathways in StSNP allows a researcher to examine possible disease-related pathways associated with a particular nsSNP(s), and link the diseases with the current available molecular structure data. The server is publicly available at http://ilyinlab.org

 

SEDB, Structural Exon Database. SEDB is an application that allows users to retrieve the exon/intron organization of genes and map the location of the exon boundaries and the intron phase onto a multiple structure alignment. SEDB is linked with Friend, an integrated analytical multiple sequence/structure viewer, which allows simultaneous visualization of exon boundaries on structure and sequence alignments http://ilyinlab.org

 

Software development skills/experience

 

General: almost 20 years of programming experience, almost 10 years in leading software development projects including all the public resources presented on the web site and also:

C/C++  ~200,000 or more lines of code on variety of different projects, 1988 - current

Java    ~100,000 lines; 2000 - current

Fortran  ~1.5 MB of code, 1995 - 2000

Perl/HTML/XML/PHP    ~ 100,000 lines, 2000 - current

MySQL:   design and development of several large DBs, MODBASE, LigBASE, DBAli, TOPOFIT-DB, SEDB, StSNP; available on the web. Development of large-scale pipelines on a number of multi-node clusters to feed the DBs. 100,000,000s of calculations.

OS: Linux/Unix, Windows, Mac X, networking, multi-core cluster.

 

Statistical: ROOT, SPSS, Matlab, R.

 

Computational biology/Bioinformatics software:

MODELLER (participated in development for 2.5 years), Swiss-MODEL.

Macromolecular visualization: RasMol, DeepView (SwissPDBViewer), MolMol, Chimera, PyMol, have developed powerful analytical-visualization package software Friend (~20 MB of code in C++/Java/Perl)

Molecular Dynamics: GROMOS, NADM/VMD, Amber/CHARMM force field

 

Crystallography software: CCP4, Xplor/CNS, O, QUANTA, MICE, etc.

 

 

Research overview

There are three main objectives:

Theoretical-computational research, a combination of theoretical developments in understanding the underlying principals of molecules in biology, their interactions assembly and functionality with the large-scale analyses and generalizations toward biological systems functionality,

Application of all available Bioinformatics/Biostatistics and Computational Biology tools to address real biomedical problems in collaboration with experiment,

Tools development, including computer applications, web servers, databases and other resources.

 

My research interest is functionality of organism at molecular level, which includes protein-protein protein-RNA and DNA-protein interactions along with ligand- protein interactions, protein structure comparison, protein classification and functionality, sequence-structure-function relationship, analysis of genome variations, integration sequence, structure, expression and metabolic information to better understand molecular basis of diseases.

I am very open to collaborations with experimental labs and have successfully accomplished a number of collaborative projects with biologists, chemists and programmers, please see the list of publications; professional in large-scale bioinformatics data analysis, including DNA/RNA and protein sequences, their variation, protein structures and their complexes and interactions.

 

Previous contributions

 

Protein X-ray crystallography: Participation in solution of 8 PDB structures. Highlight: solution of ligand-free structure of tryptophanyl-tRNA synthetase (TrpRS) (including original building the protein model into electron density), refinement; work on Maximum Entropy Method for Refinement of Protein Structures and application of it towards the solution of TrpRS. Major contribution to X-ray solution of several other TrpRS complexes.

 

Protein – ligand interactions: Development of a database of families of aligned ligand binding sites in known protein sequences and structures, LigBase;  StSNP, TrpRS complexes, TOPOFIT-THEMATICS structure based active site prediction, Modeling of enzymes involved in sterol/isoprenoid biosynthesis

 

Prediction of protein-protein interfaces and Molecular Dynamics analysis: Interaction between AP-ENDO and POL-BETA binding with DNA in the DNA-repair mechanism.

 

Genome variations: Integration of protein structure, nsSNPs and metabolic pathways into public web server StSNP.

 

Protein alignments: Development of an original objective method for protein structure comparison, TOPOFIT; application of the TOPOFIT method to comparison of all available structures in PDB and development and maintenance of web based database of structure alignment, TOPOFIT-DB, along with one-to-all web based and email based T-server. Classification of protein domains based on TOPOFIT method.

 

Bioinformatics toolbox: Integrated Front-End application for multiple structure visualization and multiple sequence alignment, Friend, with over 200 functions, it is a bioinformatics application designed for simultaneous analysis and visualization of multiple structures and sequences of proteins and/or DNA/RNA. The application provides basic functionalities such as: structure visualization with different rendering and coloring, sequence alignments, and simple phylogeny analysis, along with a number of extended features to perform more complex analyses of sequence structure relationships, including: structure alignment of proteins, investigation of specific interaction motifs, studies of protein-protein and protein-DNA interactions, and protein super-families.

 

Protein structure prediction Large–scale comparative modeling pipeline, a database for protein models, MODBASE; on modeling of genomic variations leading to non-synonymous SNPs in StructureSNP web server; tools for modeling – real-time alignment with multiple alignments and modeling through Friend software.

 

 

 



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