C372_L12 - Molecular Modeling: Conformational Molecular...

Info iconThis preview shows pages 1–10. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Molecular Modeling: Conformational Molecular Field Analysis (CoMFA) C372 Dr. Kelsey Forsythe CoMFA Cramer and Milne (1979) Comparison of molecules by alignment and field generation Wold (1986) Proposes using PLS instead of PCA for overrepresented (1000s of field non-orthogonal variables) problem (correlate field values with activities) Cramer, Patterson and Bunce (1988) Introduced CoMFA CoMFA Assumptions Activity is directly related to structural properties of system Structural properties determined by non- bonding forces Outline of CoMFA Hypothesize mechanism for binding Structure of binding site Most important/difficult Find equilibrium geometry Construct lattice or grid of points Compute interaction of probe with molecule at each point Apply PLS Predict CoMFA Structural Focus Hypothesize mechanism for binding Structure of active site and/or common pharmacophore between all compounds Most important/difficult Structural errors propagate to later stages Superpose structures SEAL Similarity index CoMFA Structural Focus Poor alignment Better alignment CoMFA Equilibrium Geometry Find equilibrium geometry Ab Initio, Semi-Empirical or Molecular Mechanics Method depends Size Accuracy CoMFA Lattice Construction Construct lattice or grid of points for field analysis Steroid (1 representative conformer shown) 14 x 11 x 7 = 1078 points CoMFA Field Data Generation Compute interaction of probe with molecule at each point Interaction is typically non-covalent (e.g. non-bonding forces) Steric, electrostatic and hydrophobic Probe depends on interaction Kim et. al....
View Full Document

Page1 / 40

C372_L12 - Molecular Modeling: Conformational Molecular...

This preview shows document pages 1 - 10. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online