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 template CA-CA distance Native CA-CA distance

http://dasher.wustl.edu/tinker/

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…

Sample.key & Parameter file … … …

Comparison between modeller & tinker structure 1fdx (modeller) 1fdx (tinker) TM-Score : 0.9633 superpose

Main work of our group project ■ Energy = E ster + E rst + E dfire bond, angle, dihedral, van der waals….. Ca-Ca dist, torsion…. ■ Minimization LBFGS (limited memory BFGS) algorithm is a member of the broad family of quasi-Newton optimization method ■ initial structure study Extended structure & Modeller structure

What is DFIRE ? ■ statistical pair potential energy function ■ developed by Zhou (University of New York, USA) N exp (i,j,r) = (r/r cut ) a (△r/△r cut )N abs (i,j,r cut ) ■ N exp : expected number of non-interacting atomic pair ■ r cut : cutoff distance in the reference state ■ N abs (i,j,r) : observed number of the same atomic pairs ■ a : given constant

A problem with dfire energy function ■ We used cubic spline algorithm to get a consecutive value.

Initial structure & Energy function test ① E = E ster + E rst Extended structure Minimized structure ② E = E ster + E rst Minimized structure Modeller structure ③ E = E ster + E rst + E dfire Modeller structure Minimized structure

① E = E ster + E rst Extended structure Minimized structure TM-score : 0.8687

② E = E ster + E rst Minimized structure Modeller structure TM-score : 0.8823

③ E = E ster + E rst + E dfire Modeller structure Minimized structure TM-score : 0.8836

Conclusions & Discussions 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. 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

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