Download pps (recommended)

Protein Planes
Bob Fraser
CSCBC 2007
Overview
• Motivation
• Points to examine
• Results
• Further work
Cα trace problem
• Given: only approximate positions of the
Cα atoms of a protein
• Aim: Construct the entire backbone of the
protein
– This is an open problem!
Cα trace problem
• Why do it?
• Some PDB files contain only Cα atoms.
• Refinement of X-ray or NMR skeletons.
• More importantly, many predictive
approaches are incremental, and begin by
producing the Cα trace.
Cα trace problem
• Possible solutions:
– De novo, CHARMM fields (Correa 90)
– Fragment matching (Levitt 92)
– Maximize hydrogen bonding (Scheraga et al. 93)
• Idealized covalent geometry
– Used by Engh & Huber (91) for X-ray crystallography refinement
– Supplemented by including additional information (Payne 93,
Blundell 03)
• All methods achieve <1Å rmsd, ~0.5Å rmsd is good.
• Perhaps including more information about the plane
could further improve results.
Idealized covalent geometry
The task
• Survey the structures in the PDB, and
determine how close the known structures
adhere to these values.
• Next look at the relationship between the
planes and secondary structures
– Is this information useful?
– If so, could it be used in refinement?
Length of plane (Cα – Cα distance)
• The so-called bond distance when given a
Cα trace.
• If all bond angles and lengths are fixed,
this distance should also be constant.
• Let’s check this distance in the PDB, and
determine the average, standard
deviation, maximum and minimum values
found.
cis vs. trans
Secondary Structure
Angle between helix axis and plane
• It is assumed that the planar regions for
amino acids in a helix are parallel to the
axis of the helix.
• Let’s put this to the test!
• How do we measure the axis of helix?
– It is a subjective measure
– We’ll use the method of Walther et al. (96), it
provides a local helix axis
Plane-axis angle
• Now we have a peptide plane and the
helix axis, so we can find the angle
between them easily.
• This same method could be applied to
beta strands and 3-10 helices.
• We should expect that some pattern
should arise since beta strands are have
regular patterns, particularly when in beta
sheets.
Data Analysis
• Use the entire PDB database as a source
• Compare the results obtained to the
expected values for the plane lengths and
alpha helices
• Determine whether a preferential
orientation exists for beta strands and 3-10
helices
Plane length
• trans and cis cases need to be distinguished
because they are different inherently
• Plane length is composed of 5 elements of
idealized covalent geometry
α-helix
3-10 Helix
β-strand
Results
Future Work
• Develop algorithm for using secondary
structure to solve trace problem.
• Test it on proteins with perfect Cα traces to
verify the accuracy of reconstruction.
• Test on randomized Cα traces.
• Integrate this information with refinement
Thanks!
Selected References
– M.A. DePristo, P.I.W. de Bakker, R.P. Shetty, and T.L. Blundell.
Discrete restraint-based protein modeling and the C -trace
problem. Protein Science, 12:2032-2046, 2003.
– A. Liwo, M.R. Pincus, R.J. Wawak, S. Rackovsky, and H.A.
Scheraga. Calculation of protein backbone geometry from alphacarbon coordinates based on peptide-group dipole alignment.
Protein Sci., 2(10):1697-1714, 1993.
– G.A. Petsko and D. Ringe. Protein Structure and Function. New
Science Press Ltd, London, 2004.
– D. Walther, F. Eisenhaber, and P. Argos. Principles of helix-helix
packing in proteins: the helical lattice superimposition model.
J.Mol.Biol., 255: 536-553, 1996.
Walther axis calculation