A DISCUSSION ON

SHARPEN SOFTWARE IN
DESINING NEW PROTEIN
MOLECULE
By- Suchismita patra
6th sem, 3rd year.
INTRODUCTION
• SHARPEN: Systematic Hierarchical Algorithms for Rotamers
and Proteins on an Extended Network.
• The intrinsic properties of folded or misfolded proteins are largely
derived from the final three-dimensional conformation of the chain.

• Computational prediction of protein structures can be used to

circumvent traditional experimental methods or to augment speed
and/or accuracy.

• In this work, we introduce two software resources aimed to allow rapid

prototyping and scaling of candidate computational structural biology
algorithms that rely upon combinatorial optimization
 Continue…
• Algorithms for discrete optimization of proteins play a central role in recent advances in protein
structure prediction and design

• SHARPEN, a framework for scaling CHOMP scripts to many computers.

• These tools allow users to develop new algorithms for a variety of applications including
protein repacking, protein-protein docking, loop rebuilding, or homology model
remediation.
Code Availability
• The core of the software is a new open-source library called
CHOMP (Combinatorial Hierarchical Optimization for
Macromolecular Problems).
• When packaged for scalable distribution, then it refer to the
program as SHARPEN (Systematic Hierarchical Algorithms for
Rotamers and Proteins on an Extended Network).
• SHARPEN currently consists of the CHOMP library code
 ROLL OF SHARPEN SOFTWARE
High resolution structure prediction
current laboratory techniques for determining
protein structure, X-ray crystallography and NMR
spectroscopy, are relatively slow, expensive and
often difficult to perform.

researchers have been working for several

decades to design efficient algorithms to predict
protein tertiary structure from the corresponding
primary amino acid sequence.
 Continuation…

• The modern approach is to sample the protein's vast conformational space,

looking for likely structures.

• As an alternative to ab initio protein structure prediction (straight from an

unfolded amino acid chain), it is often possible to start from an approximate
homology model.

• In principle, one can then refine the structure until it is close to that of the
real protein.
Continuation…
Loop rebuilding
• Loop rebuilding is an important problem in its own
right.

• Traditionally this is called loop rebuilding

because it is the loops (non alpha helical and
non beta sheet residues) that are the target.
There are specialized sampling methods for
building prospective loop coordinates.
SHARPEN implements a variant of CCD
(cyclic coordinate descent).
 Continuation…
Hierarchical structure refinement

• SHARPEN is an extensible platform

for testing combinatorial
optimization algorithms at the side
chain and backbone level on
Folding home.
• There are special challenges
associated with formulating protein
structure refinement in terms of a
discrete backbone search space,
but benefits as well.
REFERENCE
• http://www.engr.colostate.edu/~cdasnow/sharpen/sharpenabo
ut.html (accessed on 14th april )
• SHARPEN—Systematic Hierarchical Algorithms for Rotamers and
Proteins on an Extended Network, ILYA V. LOKSHA, JAMES R.
MAIOLO III, CHENG W. HONG, ALBERT NG, CHRISTOPHER D.
SNOW(Accepted 5 December 2008) DOI 10.1002/jcc.21204
Published online in Wiley InterScience
(www.interscience.wiley.com)
ACKNOWLEDGEMENT
• I am utmost grateful to Dr. Angshuman Lahiri for giving me an
opportunity to conduct a study on SHARPEN software for protein
binding.