If the last century in Science belongs to Physical Sciences then this century must belong to Life Sciences with many breakthroughs starting from DNA and proteins! The proteins are biological macromolecules that are of primary importance to all living organisms and there are various open problems including the Nobel-Prize-type problem related to protein folding. All these questions mainly depend on shape of the protein 3-D which can be summarized in terms of either the configuration of points (landmarks) or more compactly by conformational angles. Thus it has led to new tools in statistical shape analysis and directional statistics. We will discuss the following topics:-
(1) Shape alignment methods. The aim is to align different proteins using unlabelled landmarks. In this case there are new statistical alignment methods which might provide a gold standard. But how to incorporate chemical information successfully, how to compete with deterministic methods which are faster, does a hybrid method provides a solution? (2) Distribution of conformational angles. The major second problem relates to what are called Ramachandran plots which are an empirical distribution of dihedral angles summarizing the different protein shapes such as helices etc. The statistical distributions are now coming up but there are serious challenges since the distributions have unknown finite support. What directional distributions are the right one? (3) Prediction of protein structure. The third major problem is of predicting protein structure, that is, how we can predict from fragment-sequences the three dimensional local coordinates. There are various semi-deterministic solutions but we will discuss a recent probabilistic method which depends on directional statistics and hidden Markov models. The solution has a potential use in protein design, protein folding and drug discovery.
Keywords: Bioinformatics; Shape analysis; Directional statistics; Protein structure
Biography: Kanti Mardia is Senior Research Professor at the University of Leeds - a position especially created for him. He was awarded the Silver Medal of the Royal Statistical Society in 2003. The citation for the award reads “The Guy Medal in Silver for 2003 is awarded to Professor Kanti Mardia for his many pathbreaking contributions to statistical science, including two fundamental papers …, his highly acclaimed monographs and his lasting leadership role in interdisciplinary research”. He founded the Leeds Annual Statistical Research (LASR) Workshops in 1973, which have grown into international conferences. His recent research covers many new challenging fields such as Statistical Bioinformatics and several papers have been published in this areas including in PNAS, Bioinformatics, Biometrics, Biometrika, PLoS. Various biographical details up to 2000 can be found in the interview “The Guy Medal in Silver for 2003 is awarded to Professor Kanti Mardia for his many pathbreaking contributions to statistical science, including two fundamental papers …, his highly acclaimed monographs and his lasting leadership role in interdisciplinary research”, (2002) Statistical Science, and subsequent details are on his web page.