Research - Kresten Lindorff-Larsen – Section for Biomolecular Sciences - University of Copenhagen

Research profile

My research deals broadly with the relationship between protein structure, dynamics and function. We mostly use computational methods, generally integrated very tightly with experimental studies, to understand how the ability of proteins to change their shape help modulate, or indeed determines, their function. A key result from the last five years is that we have developed highly accurate models of protein biophysics, whose accuracy have e.g. enabled us to fold proteins computationally (Science, 2010 & 2011; PNAS 2012 & 2013). We have recently demonstrated that the same models allow us to describe very accurately conformational changes within folded proteins (J Chem Theory and Comput, 2014 and a manuscript in preparation). As an alternative approach, we also develop and apply methods that directly and synergistically integrate computer simulations and NMR spectroscopy (e.g. an overview in PLoS Comp Biol, 2014) and have applied such methods to describe the dynamics in both folded proteins (Nature, 2005 and manuscript in preparation) as well as unfolded and intrinsically disordered proteins (several papers). Although we are still actively involved in validating and improving the methodology, our current research is increasingly focused on applying these advances to solve complex problems in protein biophysics and biology for which direct experimental studies cannot provide the answer alone.

The combination of experiments and simulations is best performed in direct collaborations with experimentalists. Three Ph.D. students are experimentalists (and have an additional experimental supervisor) and the remaining three work mostly with computation, but in all projects experiments and simulations are tightly integrated. My group is part of the Section for Biomolecular Sciences and is closely associated with the Protein Biology Group and the Structural Biology and NMR Laboratory, an internationally recognized laboratory that, in addition to my own, consists of two groups that use experimental NMR spectroscopy to study the biology of proteins. By deliberately positioning my group within an experimental setting we aim to make our research stronger and more interdisciplinary. In addition to numerous local collaborations we have strong international collaborations including with Michele Vendruscolo (University of Cambridge, UK), Robert Best (National Institutes of Health, USA), Francesco Gervasio (University College London) and Shy Arkin (Hebrew University of Jerusalem, Israel).

Our research requires substantial computational resources, and through several grants we have been able to purchase >1000 computing cores that we have access to locally. In addition, we have access to a brand new Danish national high-performance computing facility and have, as one of the only Danish biocomputing groups, been awarded computing time (twice) via the competitive European “Partnership for advanced computing in Europe (PRACE)”. At all these sites we have access to excellent technical support, in addition to the substantial experience that has been established within my group.