Computational Methods for Protein Structure Prediction and Modeling
An ultimate goal ofmodern biology is to understand how the genetic blueprint of cells (genotype)determines the structure, function, and behaviorofalivingorganism (phenotype). At the centerofthis scientific endeavor is characterizing the bioch- ical and cellularrolesofproteins, the working molecules ofthe machineryoflife. A key to understanding offunctional proteins is the knowledge oftheir folded str- tures in a cell, as the structures provide the basis for studying proteins' functions and functional mechanisms at the molecular level. Researchers working on structure determination have traditionally selected - dividual proteins due to their functional importance in a biological process or pa- way ofparticular interest. Majorresearch organizations often have their own protein X ray crystallographic orlandnuclearmagnetic resonance facilities for structure - termination, which have been conducted at a rate ofa few to dozens ofstructures a year. Realizing the widening gap betweenthe rates ofprotein identification (through DNA sequencing and identificationofpotential genes through bioinformatics an- ysis) and the determinationofprotein structures, a numberoflarge scientific init- tives have been launched in the past few years by government funding agencies in the United States, Europe, and Japan, with the intention to solve protein structures en masse, an effort called structural genomics. A number of structural genomics centers (factory like facilities) have beenestablishedthat promise to produce solved protein structures in a similar fashion to DNA sequencing.
Presents a comprehensive overview of protein structure prediction methods Each chapter is a self contained review designed to cover (1) definition of the problem and an historical perspective, (2) mathematical or computational formulation of the problem, (3) computational methods and algorithms, (4) performance results, (5) existing software packages, and (6) strengths, pitfalls, challenges, and future research directionsCovers topics from De novo methods of protein structure prediction to structure based drug design