computer modeling in molecular biology.pdf

2 Modelling Protein Structures 13State of ProteinStructurePredictionSequence same as protein ofknown sbucture in differentstate of ligation’ Sequence differs from proteinsN of known smcture only atp pint mutationsUT Sequence differs Fromproteins of known structureonly in loop regionsSE Sequence closely related ( ~ 0 %residue identity) to at least oneQ protein of known structureUE Sequence distantly relsled toseveral proteins of known structureNCE Squence related to many sequencesbut none of known structureSequence unrelated to any otherknown sequenceOUTPUT PREDICTIONHigh resolution Rough model General Fold Scoondary StructureCoordinate Set (3-D Structure) (2-D Structure) (I-D Structure)--+Energy minimizationmolecular dynamicsn-D prediction I 1-D predictiona--+Specialized homology modellingConformational searching----+ IGeneral Homology modelling I--+ ’Structural information ‘threading’. Motifs (pmsite) Im m 1 1 1 m m m 1 1 m 1 1 =No Structural Information7====+--T---Predicted interactions between Secondary Structuresecondary structural units I PredictionIIFigure 2-1. An overview of the state of the art in structure prediction. This figure is organisedinto different categories of potential input information and different categories of potentialoutput information. It describes the dependence of the quality and extent of detail of possibleinferences, on the information available when undertaking a modelling project. The terms 1-42-D and 3-D structure under “Output Prediction” refer to the information predicted: 1-Dmeans that only the structural state (e. g. a-helix, P-strand, turn, coil) of a residue is predicted.2-D means that a list of interactions to each residue is predicted (e. g. contact map). 3-D meansthat the geometry of interactions of each residue is predicted (e. g. full threedimensionalmodel). Note that the prediction of 1-D information may involve contributions from 2-D information(e. g. Secondary Structure Prediction (I-D) involves i - i - n . . . i - i + n terms).confidence. This is a restatement of the protein folding problem outlined in Section2.1.2. What is interesting is how the dashed lines are moving: For the input thehorizontal is moving with respect to the proportion of the sequences of unknownstructure which lie on each side. Progress is being made in aligning all known proteinsequences to at least one known structure, as the sensitivity of the aligment programsimproves and the database of known structures increases in size. A recent test caseanalysis of the 182 proteins identified in Yeast chromosome I11 [lo, 111 showed that