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RAM SAMUDRALA |
Large Scale Protein Structure Prediction Using Comparative Modeling and ab initio Techniques |
The goal of this project is to provide as much structural information
as possible for new sequences that are being determined, including modelling
complete genomes of organisms, using ab initio and comparative modelling
methods. These methodologies that were developed were tested in a bona-fide
manner at the third meeting on the Critical Assessment of Protein Structure
Prediction (CASP3) in December 1998. |
The following tasks have been accomplished in this area: |
Enhancement of conditional probability discriminatory function to
better discriminate native from non-native conformations. This includes
using combination functions and devising a new non-local packing function.
This was tested at CASP3 with positive results (see publication list). A database of incorrect protein conformations, called Decoys ìRî
Us (http://dd.stanford.edu) was developed to aid in development of discriminatory
functions. Enchancement of side chain generation algorithm to better position
sidechains. This was tested at CASP3 with positive results (see publication
list). Developed an exhaustive main chain sampling algorithm for loop prediction,
in conjunction with the graph theoretic-approach. This was tested at CASP3
with positive results (see publication list). In addition, a semi-database
approach based on fragments from a library of protein structures has been
developed. This will be tested at CASP4. Developed a build-up procedure for fitting secondary structure onto
lattice models. This was tested at CASP3 with positive results (see publication
list). Various collaborations for structural and functional genomics studies,
including predicting structures for ORFs in the yeast genome and guiding
experimental studies using predicted structure.
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Future plans include building large number of models for well-characterised
families, improvement of ab initio technique by using a fragment based
simulated annealing approach for predicting structure, and improvement
of discriminatory functions. |
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