Introduction To Structural Bioinformatics - NCBR

Structural Bioinformatics(C3210)Introduction toStructural Bioinformatics

Structural BioinformaticsStructural Bioinformatics is an interdisciplinary field that dealswith the three dimensional structures of biomolecules. It attemptsto model and discover the basic principles underlying biologicalmachinery at the molecular level. It is based on the assumptionthat 3D structural information of a biological system is the core tounderstanding its mechanism of action and function. Structuralbioinformatics combines applications of physical and chemicalprinciples with algorithms from computational science.Major areas: protein and nucleic acid 3D structure determination prediction of protein 3D structure from sequence protein structure validation protein structure comparison and alignment protein and nucleic acid structure classification inferring protein function from structure prediction of protein-ligand interaction prediction of protein-protein interactions development of databases2

Challenges in the Post Genomic EraThe completion of the human genome project (first draft 2000,completed 2003) and other genome projects were the first steptowards a comprehensive understanding of life at the molecularlevel.One of the key issues is the characterization of structure andfunction of proteins with a view to using the findings in thediscovery of novel and effective therapeutic treatments.3

Structure-function paradigmStructural Bioinformatics is based on the proteinstructure‑function paradigm, which states that the function of amacromolecule is dictated by its 3D-structure.The challenges for our post genomic era towards a systematicunderstanding of life are: to obtain the 3D structures of all the proteins encoded in thegenomes to decode their function based on their structure4

Solved 3D Structures GrowthTotal number of determined 3D structures of proteins isapprox. 156 000 (September 2019)5

Is Structure Sufficient to Predict Function?Proteins are not static; to fulfill their function they undergo a widerange of motion and conformational rearrangements. Theknowledge of a static structure may not be sufficient tounderstand its biological function. An important component ofstructural bioinformatics is the development of experimental andcomputational methods (such as molecular dynamics) that shedslight on the dynamic behavior of biological systems. Thesemethods simulate the way biomolecules behave, specificallyrecognize each other, interact and trigger biological events at themolecular level.6

Biomolecules in the CellThe two most important biomolecules present in our cells areproteins and nucleic acids.7

ProteinsProteins form the very basis of life. They are the most abundantmacromolecules in living cells. Thousands of different proteins canbe found in a single cell, and proteins have been identified in allparts of all cells. Proteins affect virtually every property thatcharacterizes a living organism.8

Structural Diversity of Protein StructureThe great diversity of the functional properties of proteins isdirectly related to their subtle three-dimensional structures. Everyprotein has a unique 3D structure that determines its function.9

Nucleic AcidsNucleic acids are the information carriers in the cells. Thisinformation is stored in the form of long polymer chains. Althoughthe information they carry is one-dimensional, it is essential tounderstand the 3D structure of nucleic acids. This structuredictates their organization, functions and interactions withproteins.Structure of DNA ismade of two helicalstrands ofpolynucleotides.Due to its nature, thishelix contains grooveswhich are preferredsites for proteins andother molecules tointeract with the DNA.10

that 3D structural information of a biological system is the core to understanding its mechanism of action and function. Structural bioinformatics combines applications of physical and chemical principles with algorithms from computational science. Major areas: protein and nucleic acid 3D structure determination prediction of protein 3D .