Keynotes

Clustal Omega and multiple sequence alignments

Des Higgins, Professor of Bioinformatics in University College Dublin, Ireland

Multiple Sequence Alignments (MSA) are used to take a set of related DNA or protein sequences and line them up so as to make them easy to compare to each other. Most MSAs are made using a range of related heuristics that involve clustering the sequences and building an alignment that follows the clusters. These methods have served us well for the past 25 years but are now starting to creak. I will describe a new program called Clustal Omega which can make alignments of very large numbers of sequences. It gives good quality alignments in reasonable times and has extensive features for adding new sequences to or for exploiting information in existing alignments. It is available for download from www.clustal.org in a command-line driven format (Linux style) for proteins only. It is also available for on-line use from the EBI.

Biography

Prof. Des Higgins has a PhD in Zoology from Trinity College Dublin, Ireland. His lab currently maintains and develops the Clustal package for multiple sequence alignment in collaboration with groups in France, Germany and the UK. He wrote the first version of Clustal packages in 1988 and then moved to the EMBL Data Library group, in Heidelberg, in 1990 as a post-doc and later, staff scientist. In 1994, he moved to the EBI, Hinxton with the Data Library and stayed there for two years. This coincided with the release of Clustal W, and later, Clustal X which became extremely widely used and cited. Currently his team is working on Clustal Omega which is designed for making extremely large protein alignments.


A Mechanistic Structural View of Ras Biology

Ruth Nussinov, Cancer and Inflammation Program, National Cancer Institute and Medical School, Tel Aviv University

Ras proteins are small GTPases that act as signal transducers between cell surface receptors and several intracellular signaling cascades. KRas4B is among the frequently mutated oncogenes in human tumors. Ras proteins consist of highly homologous catalytic domains, and flexible C-terminal hypervariable regions (HVRs) that differ significantly across Ras isoforms. We have been focusing on key mechanistic questions in Ras biology from the structural standpoint. These include whether Ras forms dimers, and if so what is their structural landscape; how do Ras dimers activate Raf, a key Ras effector in a major signaling pathway; what is the role of calmodulin is Ras signaling, what is the potential regulatory role of the hypervariable region and its membrane anchoring and what are the mechanisms of oncogenic mutations. We believe that structural biology, computations and experiment, are uniquely able to tackle these fascinating and important questions.

Biography

Prof. Ruth Nussinov has a entense career with many achievements. After completing her Ph.D. in Biochemistry from Rutgers, she became a fellow at the Weizmann Institute. She was a visiting Scientist at the Berkeley and Harvard. In 1985, she joined Tel Aviv University as Associate Professor and became Full Professorin 1990. Her association with the NCI also initiated in 1985.

Nussinov's 1978 paper proposed the dynamic programming algorithm for RNA secondary structure prediction which is to date the leading method in this field. She also pioneered DNA sequence analysis in the early 1980s. In 1999, her NCI group proposed the model of 'conformational selection and population shift' as an alternative to ‘induced fit’ to explain molecular recognition. This paradigm has impacted the scientific community's views and strategies in drug design, biomolecular engineering, and molecular evolution.

Ruth Nussinov was a recipient of the 2011 Biophysical Society Fellow Award for her extraordinary contributions to advances in computational biology on both nucleic acids and proteins. She has coauthored over 440 scientific papers and is highly cited. Her research mainly focuses on protein structure, dynamics, function, protein–protein interactions, and cellular signaling.