Bioinformatics

BioinformaticsAyesha M. Khan

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Structural BioinformaticsStructure study is an abstraction

All which we study is an abstraction to make comprehension of a complex entity more straightforward

Structure is better conserved than sequence

It can adopt a wide range of mutationsPhysical forces favor certain structures

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Protein structure basics

•It is the amino acid sequence that “exclusively” determines the 3D structure of a protein• 20 amino acids – modifications do occur post translationally

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It is the properties of the R group that determine the property of the AA and ultimately the proteinDifferent schemes exist for describing the propertiesHydrophobicity, polarity and charge are common measures

Chirality – amino acids are enatiomorphs, only the L form is found in naturally forming proteins. Some enzymes can produce D amino acids

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Amino acid classification

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Peptide bond• Individual amino acids form a polypeptide

chain• Such a chain is a component of a hierarchy for

describing macromolecular structure• The chain has its own set of attributes• The peptide linkage is planar and rigid

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Geometry of the chainA dihedral/torsion angle is defined by four consecutively bonded atomsThere are three repeating torsion angles along the backbone chain called phi, psi and omega.

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Geometry of the chain (contd)

Omega is the rotation around the peptide bond it is planar and is 180 under ideal conditions

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Ramachandran plotThe values of phi and psi are constrained to certain values based on steric clashes of the R group. Thus these values show characteristic patterns as defined by the Ramachandran plot.Plot of Psi vs Phi is called a Ramachandran plot (after G. N. Ramachandran) or conformational map.

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Ramachandran plot (contd)

White areas correspond to conformations which are sterically disallowed for all amino acids except glycine which is unique in that it lacks a side chain.The red regions correspond to conformations where there are no steric clashes:i,.e.,these are the allowed regions namely the alpha-helical and beta-sheet conformations. The yellow areas show the allowed regions if the atoms are allowed to come a little closer together.