Poster Presenter

Solvation Effect On Biomolecules For Drug Discovery
Sehan Lee, Change Joon Lee, Kwang-Hwi Cho, And Kyoung Tai No
Korea

Background: Most Biological Phenomena Take Place In Solvent And The Solvent Effects Modulate Biomolecular Dynamics And Energetics. Whenever Macromolecules Act On A Living Body, Solvent Has A Dramatic Effect On The Conformational Equilibria, The Aggregation Of Hydrocarbons In Water, Which Is Central To The Folding Of Biopolymers, And Binding For Host-Guest Complexes, As Well As Enzyme Catalysis. The Description Of Solvation Effect On Solute Molecule In Molecular Scale Is A Very Hard Task, Because Of Enormous Degree Of Freedom In Solution, Which Leads To Various Approximated Approaches. Continuum Solvent Approach, An Appealing Alternative To Explicit Solvent Approach, Does Not Provide Atomic Resolution Of Individual Solvent Molecules, But It Significantly Improves The Computational Speed And Reduces Errors In Statistical Averaging That Arise From Incomplete Sampling Of Solvent Conformations.

Methods: The Generalized Solvation Free Energy Density (G-SFED) Model, An Advanced Model Of SFED Model Proposed By No Et Al., Is Developed To Compute The SFED At A Point On Cavity Surface In Any Environment. The SFED Is Described As A Linear Combination Of Basis Functions, Evaluated By Summing The Interaction Energy Between Each Atom Of The Solute With A Grid Point In The Solvent. These Basis Functions And The Linear Expansion Coefficients Is A Function Of Some Physical Properties Of The Solute Solvent, Respectively. The Parameters Were Determined By Minimizing The Error Between The Calculated And Experimental Solvation Free Energy With 2105 Free Energies Of Solvation Of The Neutrals In 80 Solvent And 90 Ionic Hydration Free Energies.

Result And Conclusion: The Mean Absolute Error For Solvation Free Energies Of 2105 Neutrals And Ions Are 0.44kcal/Mol And 1.42kcal/Mol, Respectively. Since The Biological Medium Is Not A Single Solvent, The Complex Of Biomolecules, We Apply The G-SFED Model To The Mixture Solvent And Get A Good Result With Small Available Data Set. The Final Target Of G-SFED Model Is The Prediction Of Molecular Properties And Metabolism Of Drug Molecules In Biological System.