Kepp Research

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Method development: OPLS force fields

Electrostatic interactions dominate proteins structure and dynamics, but anions and cations
were not on the same "free energy scale" in common force fields. Thus, in 2006 and 2008
we developed OPLS force fields with consistent free energies optimized from experimental
data for both anionic and cationic charged groups, which should be considered together
(think e.g. on a salt bridge dissocating). Since then, others have followed similar lines.

(non-bonded parameter files for Gromacs MD simulation)


OPLS-2006
Jensen, K. P. & Jorgensen, W. L. 2006

OPLS-2008/TIP4P
OPLS-2008/TIP3P
Jensen, K. P. 2008

Note that the protein force field OPLS-2008 depends on the water model.
The protein-water system should be thought as a whole complete system, they cannot be separated.
TIP3P and TIP4P give very different charged solute hydration!

Thus I defined the concept of "water-optimized protein force fields", particularly important for charged groups.


More details can be found here.



Some discoveries

Medicinal and Molecular Biochemistry
The zinc cascade of Alzheimer's Disease identifying new approaches and targets for treating the disease 

Alzheimer Theories

The "broad crossing mechanism" of oxygen binding and activation by heme, a process crucial to all major life forms on this planet but formally forbidden by quantum mechanics (together with Ulf Ryde, Lund University) 

O2 binding

K. P. Kepp, Coordination Chemistry Reviews, 2017
"Heme: From quantum spin crossover to oxygen manager of life"

Presenilins:
The dynamic mechanism of presenilin function; the most complete structure of presenilin 1, the main genetic risk factor and drug target of Alzheimer's disease





A. K. Somavarapu, K. P. Kepp*, Neurobiol. Disease 2016, 89,
147-156. "The dynamic mechanism of presenilin-1 function: Sensitive gate dynamics and loop unplugging control protein access"

A. K. Somavarapu, K. P. Kepp*, J. Neurochem. 2016, 137, 101-111. "Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease"

The loss of function theory of Alzheimer's disease



K. P. Kepp*, Progress in Neurobiology, 2016, 143, 36-60.



Fundamental Physical Inorganic Chemistry
The thermochemcial spin series (a new series that complements the spectrochemical series of inorganic chemistry)



S. R. Mortensen, K. P. Kepp*, J. Phys. Chem. A 2015, 119, 4041-4050.
Oxophilicity and thiophilicity (first scale defined for the periodic table)







K.P. Kepp, Inorg. Chem 2016.




Density Functional Theory
Mapping the direction and magnitude of systematic effects in theoretical chemistry to obtain chemical accuracy
DFT use

K. P. Kepp*, Inorg. Chem. 2016, 55, 2717-2727. "Theoretical Study of Spin Crossover in 30 Iron Complexes"