1. Database extraction of residue-specific empirical potentials
building a complete set of energy parameters including distance and angle dependence of inter-residue interactions
estimation of secondary structure propensities of amino acids
utility in fold recognition, homology modeling and/or threading
11/11/2018

2. Underlying principle: Inverse Boltzmann law
Energies --> Probabilities (Boltzmann)
Probabilities --> Energies (inverse Boltzmann)
Boltzmann law: Pi ~ exp (-Ei/RT)
Inverse Boltzmann: Ei = -RTlnPi + ct

3. Two types of interaction: Long-range Short-range
(close in space, not in sequence)
Short-range
(sequential neighbors)
Long-range are the most important dominant interactions in folding

4. Residue-specific interactions
Interactions of hydrophobic residues
Interactions between charged/polar residues

5. Residue-Residue Interactions (from Protein Structures)
Effective solvent-mediated contact potential = exy + e00 – ex0 – eyo

6. Residue-specific distributions of # of neighbors
0.0
0.1
0.2
0.3
Tot
Gly
Ala
Leu
Glu
Pro
Frequencies 15 10 5
# Neighbors

7. Short-range (bonded) interactions
Coupling between consecutive dihedral angles in the virtual bond model

8. Abscissa values from helix-coil transition [O'Neil and deGrado (1990)]
Comparison of predicted and experimental helical propensities
0.2
0.4
0.6
0.8
-0.2 A M
) (kcal/mol) L Q Y I  F -  F , V  S +  C ( N W
A-GLY T
- E G -  G
(kcal/mol) 
Abscissa values from helix-coil transition [O'Neil and deGrado (1990)]
For more info...
Bahar, Kaplan and Jernigan, Proteins 1998

9. Experimental (abscissa) values from [Kim and Berg (1993)]
Comparison of predicted and experimental b-strand propensities 1
1.5 2
2.5
0.3
0.35
0.4
0.45
0.5
0.55
0.6 E X (  + , -
) = 
G R= 0.90 I V C F
)/RT Y L -   , M W  + K T  D ( H A Q
- E R N E S A -  G
(kcal/mol) 
Experimental (abscissa) values from [Kim and Berg (1993)]

11. Multi-body geometry-dependent interactions?
Long distance effects can be taken care by ‘whole sentence exponential model”.
Spatial, not sequential, correlations are important in controlling folding, misfolding, interactions.
Can we select features/attributes that characterize the 3-d topology of contacts?
Multi-body geometry-dependent interactions?
Keskin, O. , Bahar, I. , Badredtinov, A., Ptitsyn, O. B., & Jernigan, R. L. Protein Science 7, , 1998.