Kepp Research

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Research interests and some accomplishments:

Fundamental physical, biological and inorganic chemistry: Laws of thermodynamics and quantum mechanics applied to chemical problems of importance. For example, a scale of oxophilicity (2016)
. The function of heme. The mechanism, relativistic effects and entropy-enthalpy compensation of spin crossover (2013-). Finding new accurate hydration free energies of metal ions from thermochemical cycles. Benchmarking and understanding DFT methods.

Protein science and theoretical biochemistry: The structure, dynamics, function, and natural evolution of proteins.

Goals:  To identify and combat the molecular causes of neurological diseases such as Alzheimer's Disease.


2016: The Loss of Function theory of Alzheimer's Disease.

2016: The gate-plug mechanism whereby mutations in presenilin 1 cause Alzheimer's Disease: Loss of hydrophobic packing and stability in the membrane reduces cleavage accuracy. The properties lost by mutation correlate to clinical severity of PSEN1 variants.

2015: The structure of β-amyloid in best agreement with available experimental data, from comparison of 21 force field methods.

2015: The Energy Theory of Neurodegeneration. Neurodegeneration in ALS can be due, not to a specific toxic molecular mode of protein aggregation but to systemic energy burden of protein turnover. This increased energy cost correlates with patient data.

MAIN EARLY DISCOVERIES 2003-2009 (all as first author):

2003: Explaining molecular co-evolution of metal ions and tetrapyrrole cofactors from thermodynamic stability and function (with U. Ryde).

2004: The broad crossing mechanism of ligand binding to heme, explaining how evolution of close-lying spin states in heme allows fast reversible binding of O2 crucial to life (with U. Ryde).

2005: O2 binding to heme is the basis of  ife on this planet but has been debated for 50 years. We did the first high-level calculation of this problem (multistate CASPT2), to answer the old question about the relative contributions of Pauling, Weiss, and Goddard / McClure resonance forms (with Björn Roos & Ulf Ryde).

2005: Our mechanism of how the Co-C bond is cleaved in B12-dependent enzymes. QM/MM simulations show that the Ado radical is stabilized by electrostatic interactions and the Co(III) ground state is distorted. Both effects (product stabilization and reactant destabilization) contribute (with U. Ryde).

2006: OPLS-2006 force field: First co-parameterization of anions and cations for use in molecular simulation, to make free-energy consistency critical to accuracy (with W. L. Jorgensen).

2008: OPLS-2008 force field: First demonstration of the water model --- protein force field interdependence that affects most protein simulations and two specifically parametrized OPLS force fields for charged residues, one for TIP3P water and one for TIP4P water.

January 2019: Welcome to Kalyan Jana who will help us understand protein stability
June 2018: Welcome to Budheswar, who will work on predicting Alzheimer's disease-causing mutations
May 2018: Humble thanks to DFF and the Danish taxpayers for supporting our project on protein stability
May 2018: Kasper celebrates his 100th review report for ACS since 2007
April-May 2018: Kasper is on family leave from work.
Feb 1, 2018. Ning Tang joins as DFF postdoctoral fellow working on new medicine targeting gamma secretase in Alzheimer's disease. Welcome!
Jan 1, 2018. Rukmankesh will join our group to study laccases in collaboration with Prof. Anne Meyer, DTU Chemical Engineering - Welcome!
Dec 12, 2017. Arun defends his ph.d. thesis on proteins in Alzheimer's Disease. Congratulations!
Dec 7, 2017. NNF awards us funding for our project that will explore the causes and disease properties of mutations in Alzheimer's disease. Thanks!
July 4, 2017. Kasper speaks at the EICC4 conference
May 8, 2017. Kasper will speak at the Danish Annual meeting for Neuroscience
May 8, 2017. DFF funds our research into the mechanism and new treatments targeting the protein gamma secretase (commence 2018) Thanks!
Jul 2016. Kasper speaks at the ICPP conference in Nanjing, China, on heme biochemistry.
Aug 2015. Speaking at the ECOSTBio meeting in Belgrade, Aug 24-25.
July 2015. Speaking at the ICCB conference in Kauai, Hawaii, July 2 to 6. 
June 2015. EMBO neuro- degeneration meeting in Heidelberg June 14-17. 
Nov 2014. New patent WO2014167112 for synthesizing sugars 
Oct 2014. Søren Brander defends his Ph.D.  Congratulations!
Sep 2014. Arun joins our group as a ph.d. student to work on proteins involved in Alzheimer's disease.
Dec 2013. Kasper joins the Management commitee of the COST action on spin states in biochemistry and technology

Jun 2013. Pouria Dasmeh successfully defends his Ph.D. Congratulations!

Copyright 2014. Kasper P. Kepp.

Thanks to our sponsors:

ministry    EMBODTUDCSC