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Development of Software Package for Determining Protein Titration Properties

Development of Software Package for Determining Protein Titration Properties. By Kaila Bennett, Amitoj Chopra, Jesse Johnson, Enrico Sagullo. Overview.

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Development of Software Package for Determining Protein Titration Properties

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  1. Development of Software Package for Determining Protein Titration Properties By Kaila Bennett, Amitoj Chopra, Jesse Johnson, EnricoSagullo

  2. Overview • This talk will address how our group proposes to develop a stand-alone software package capable of elucidating protein titration characteristics using the thermodynamic cycle Adapted from Morikis et al

  3. Background • It is well known that proteins are highly dependant on the pH of the environment • Functional groups within the protein can extract or release protons • This proton transfer phenomena lead to the changes in ionizable charge groups: • Aspartic acid • Glutamic acid • Arginine • Lysine • Histadine • Charge amino acids have titratable side chain groups • These titratable groups have characteritisticpKa’s

  4. Background (pKa) • The thermodynamic cycle can be used to calculate pKa • Within each pKa resides an intrinsic and apparent pKa • The intrinsic pKa describes the ionization process of a specific ionizable group when all other ionizable groups are held constant (Morikis et al). • The apparent pKa relates the intrinsic pKa and the free energies between charged residues Cycle adapted by Morikis et al

  5. Background • To extract titration properties we will be writing scripts using the programming language, R • R programming language used for statistical computing and graphics • Using R, we will be able to integrate free energy calculations using Adaptive Poisson-Boltzmann Solver (APBS)

  6. Purpose of the Project • Using R programming, we want to write a function that converts PDB files to PQR files. • Once the program is complete, we will use APBS software to calculate free energies and electric static potentials. • These calculations will then aid us in writing a program that will calculate intrinsic and apparent pKa values

  7. Objectives Winter • Get acquainted with R programming language • Workshops with Dr. Girke • Tutorial help from Chris Kieslich • Incorporation of APBS • Allows us to calculate the intrinsic pKa values • Calculates Free energies • Have software able to take any protein database files (pdb) and calculate intrinsic pKa to generate titration curves Examples of titration curves generated in R

  8. Objectives Spring • Statistical approximation for the calculation of apparent pKa values using the intrinsic values • Clustering • Monte Carlo • Add scripts to print out titration curves for each and all ionizable amino acids • Calculate protein stabilities and binding free energies Example of clustering in R

  9. Methodology Winter

  10. Methodology Spring

  11. Budget • As of now, we do not foresee any expenditures due to the fact that we are using all free software

  12. Relevant Equations

  13. Conclusion • The goal of this project is to create a local downloadable software package that will be able to calculate the titration properties for any protein • The software will first calculate the intrinsic pKa values of each residue which will then be correlated into the apparent pKa values • The software will work to generate titration curves for easy to view analysis • The software will integrate already defined software such as APBS to in essence create a user-friendly convenience package. • It will be a stand-alone software free and available for anyone to use

  14. Acknowledgements • Dr. Dimitrios Morikis • Chris Kieslich • Dr. Thomas Girke • Dr. Jerome Schultz • Hong Xu

  15. References • Trylska, Joanna. "View Continuum Molecular Electrostatics, Salt Effects, and Continuum Molecular Electrostatics, Salt Effects, and Counterion Binding—A Review of the Poisson–Boltzmann Counterion Binding—A Review." Wiley InterScience 28.2 (2007). Print • Antosiewicz, Jan M. "Protonation Free Energy Levels in Complex Molecular Systems." Wiley InterScience 89.4 (2007). Print • Gilson, Micheal K. "INTRODUCTION TO CONTINUUM ELECTROSTATICS, WITH MOLECULAR APPLICATIONS." Editorial. 13 Jan. 2006. Print • Morikis, Dimitrios. "Molecular thermodynamics for charged biomacromolecules." Fluid Phase Equilibria (2006). Print • Nielsen, Jens. "Analyzing Enzymatic pH Activity Profiles and Protein Titration Curves Using Structure-Based pKa Calculations and Titration Curve Fitting." Methods in Enzymology. Print.

  16. Questions

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