WELCOME TO OUR RESEARCH GROUP....
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.
RECENT DISCOVERIES IN PROTEIN MISFOLDING DISEASES:
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
|May 2018: Humble thanks to DFF and
the Danish taxpayers for supporting our project on
|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.
|Jan 1, 2018. Rukmankesh will join
our group to study laccases in collaboration with
Prof. Anne Meyer, DTU Chemical Engineering -
|Dec 12, 2017. Arun defends his
ph.d. thesis on proteins in Alzheimer's Disease.
|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
|Jul 2016. Kasper speaks at the
conference in Nanjing, China, on heme
|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.|