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Homology modeling by using TINKER package
The 10th Protein Folding Winter School Seungryong Heo, Juyong Lee and Keehyoung Joo
Homology Modeling Procedure
Homology modeling by using TINKER package The 10th Protein Folding - - PowerPoint PPT Presentation
Homology modeling by using TINKER package The 10th Protein Folding - - PowerPoint PPT Presentation
Homology modeling by using TINKER package The 10th Protein Folding Winter School Seungryong Heo, Juyong Lee and Keehyoung Joo Homology Modeling Procedure Query & Template sequence Alignment 1fdx CA-CA distance restrain from alignment
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Query & Template sequence Alignment
1fdx
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CA-CA distance restrain from alignment
Native CA-CA distance template CA-CA distance
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http://dasher.wustl.edu/tinker/
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Essential files before running minimization ■ sample.pdb à sample.xyz ■ sample.key à parameter file path, keyword… ■ parameter file à amber02.prm, charmm22.prm,oplsaal.prm…
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Sample.key & Parameter file
… … …
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Comparison between modeller & tinker structure
1fdx (modeller) 1fdx (tinker) superpose TM-Score : 0.9633
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Main work of our group project ■ Energy = Ester + Erst + Edfire ■ Minimization ■ initial structure study
LBFGS (limited memory BFGS) algorithm is a member of the broad family
- f quasi-Newton optimization method
bond, angle, dihedral, van der waals….. Ca-Ca dist, torsion…. Extended structure & Modeller structure
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What is DFIRE ? ■ statistical pair potential energy function ■ developed by Zhou (University of New York, USA)
Nexp(i,j,r) = (r/rcut)a(△r/△rcut)Nabs(i,j,rcut)
■ Nexp : expected number of non-interacting atomic pair ■ rcut : cutoff distance in the reference state ■ Nabs(i,j,r) : observed number of the same atomic pairs ■ a : given constant
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A problem with dfire energy function
■ We used cubic spline algorithm to get a consecutive value.
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E = Ester + Erst
Extended structure Minimized structure Modeller structure
E = Ester + Erst
Minimized structure Modeller structure
E = Ester + Erst + Edfire
Minimized structure
① ③ ②
Initial structure & Energy function test
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TM-score : 0.8687
E = Ester + Erst
Extended structure Minimized structure
①
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TM-score : 0.8823 Modeller structure
E = Ester + Erst
Minimized structure
②
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Modeller structure
E = Ester + Erst + Edfire
Minimized structure
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TM-score : 0.8836
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Conclusions & Discussions
- 1. Introduce more restraint energy terms
- N-O, Angle, Torsion, Side chain, etc.
- 2. Use more powerful optimization method
- Global optimization
- 3. Consider gap regions
- Physics and Statistical potentials
1. CA-CA restraints generated by using alignment and template provide reliable energy term to fold native like structure. 2. Tinker provides many useful functions for making structure prediction tool.
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