GBSA -And Other Bad Solvation Models

Table of contents

GBSA -And Other Bad Solvation Models

Slide 2

Generalized Born Equation

Neutral CSD Subset: ‘Modern’ GB

Slide 5

Slide 6

Original GB Test Set Revisited

From Integrals to Sums

Error Analysis of MacroModel GB

Error Analysis: GB vs PB-VdW surface

Error Analysis: Hard Sphere GB

Slide 12

Slide 13

Gaussian Generalized Born

Error Analysis: Gaussian GB

The Effect of Correct Born-Radii

Why Don’t Exact GB Radii Help?

Alternate Pair Term

Error Analysis: Alternate Pair Term

Algorithmic Complexity

Electrostatic Separation (Gaussian)

You Make The Call - I

Sheffield, Home to:

The Sheffield Solvation Model

Eighteen Blockbuster Drugs

Test System: Cyclic Urea

Sheffield vs ZAP: Cyclic Urea. Multiple Conformers (50), Single Charge Set (MMFF).

Sheffield vs ZAP: Cyclic Urea. Multiple Charge Sets (5168), Single Conformer.

Sheffield vs ZAP: Cyclic Urea. Multiple Charge Sets (5168), Single Conformer, Close up.

ZAP vs Sheffield (Tweedledum) ZAP vs GBSA (Tweedledee)

Just How Similar are They?

What About Proteins?

Protein Solvation Energy

What about Binding to Proteins?

You Make the Call - II

What about Experiment?

Can GB ever, in any conceivable, possible Universe be a ‘better’ theory than PB?

Conclusions:

Deep Appreciations to..

Author: Anthony Nicholls

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