Modelling protein tertiary structure

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Modelling protein tertiary structure Ram
Samudrala University of Washington
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Outline
1. Introduction to protein structure (15
minutes) - de novo prediction - comparative
modelling2. Introduction to RAMP software
(10 minutes) 3. Installation/set up of
RAMP software (5 minutes)4. Comparative
modelling using RAMP software (45 minutes) -
template selection (web) (10
minutes) - alignment (web)
(10 minutes) - scgen_mutate to create
initial model (10 minutes) -
mcgen_semfold_loop to build loops (10
minutes) - refinement
(5 minutes)5. Ab initio modelling using
RAMP software (45 minutes) - secondary
structure prediction (5 minutes) - setting
up simulation on a cluster (10 minutes) -
running the simulation (10-20
minutes) - break/questions - energy
minimisation (5 minutes)
- scoring using functions from RAMP (10
minutes) - final selection of native-like
conformations (5 minutes)
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Comparative modelling of protein structure
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De novo prediction of protein structure
sample conformational space such that native-like
conformations are found
hard to design functions that are not fooled by
non-native conformations (decoys)
astronomically large number of conformations 5
states/100 residues 5100 1070
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Semi-exhaustive segment-based folding
EFDVILKAAGANKVAVIKAVRGATGLGLKEAKDLVESAPAALKEGVSKDD
AEALKKALEEAGAEVEVK
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Ab initio prediction at CASP Consistently
predicted correct topology ( 4 to 6 Å) for
60-100 residues
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Comparative modelling at CASP Overall model
accuracy ranging from 1 to 6 Å for 50-10
sequence identity
T137 1.0 Å (133 aa 57 id)
T182 1.0 Å (249 aa 41 id)
T150 2.7 Å (99aa 32 id)
T160 2.5 Å (125 aa 22)
T133 6.0 Å (260 aa 14)
T185 6.0 Å (428 aa 24 id)