development of software package for determining protein titration properties
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Development of Software Package for Determining Protein Titration Properties. By Kaila Bennett, Amitoj Chopra, Jesse Johnson, Enrico Sagullo. Overview. - PowerPoint PPT PresentationTRANSCRIPT
Development of Software Package for Determining Protein
Titration PropertiesBy
Kaila Bennett, Amitoj Chopra, Jesse Johnson, Enrico Sagullo
OverviewThis 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
BackgroundIt is well known that proteins are highly dependant on the pH of the environmentFunctional groups within the protein can extract or release protons This proton transfer phenomena lead to the changes in ionizable charge groups:
Aspartic acidGlutamic acidArginine LysineHistadine
Charge amino acids have titratable side chain groups These titratable groups have characteritistic pKa’s
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
BackgroundTo extract titration properties we will be writing scripts using the programming language, RR programming language used for statistical computing and graphicsUsing R, we will be able to integrate free energy calculations using Adaptive Poisson-Boltzmann Solver (APBS)
Purpose of the ProjectUsing 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
Objectives WinterGet acquainted with R programming language
Workshops with Dr. GirkeTutorial help from Chris Kieslich
Incorporation of APBS Allows us to calculate the intrinsic pKa valuesCalculates 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
Objectives SpringStatistical 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 acidsCalculate protein stabilities and binding free energies
Example of clustering in R
Methodology Winter
Methodology Spring
BudgetAs of now, we do not foresee any expenditures due to the fact that we are using all free software
Relevant Equations
ConclusionThe goal of this project is to create a local downloadable software package that will be able to calculate the titration properties for any proteinThe software will first calculate the intrinsic pKa values of each residue which will then be correlated into the apparent pKa valuesThe software will work to generate titration curves for easy to view analysisThe 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
Acknowledgements
Dr. Dimitrios Morikis Chris KieslichDr. Thomas GirkeDr. Jerome SchultzHong Xu
References 1. 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
2. Antosiewicz, Jan M. "Protonation Free Energy Levels in Complex Molecular Systems." Wiley InterScience 89.4 (2007). Print
3. Gilson, Micheal K. "INTRODUCTION TO CONTINUUM ELECTROSTATICS, WITH MOLECULAR APPLICATIONS." Editorial. 13 Jan. 2006. Print
4. Morikis, Dimitrios. "Molecular thermodynamics for charged biomacromolecules." Fluid Phase Equilibria (2006). Print
5. Nielsen, Jens. "Analyzing Enzymatic pH Activity Profiles and Protein Titration Curves Using Structure-Based pKa Calculations and Titration Curve Fitting." Methods in Enzymology. Print.
Questions