Skip to main content


Laboratory for molecular structural dynamics

Our research activity is organized around 5 selected fundamental topics whose common concept is the underlying dynamics of complex biomolecular systems:


1) Hydrophobicity and hydration of biomolecules.

Water is an essential participant in the stability, structure, dynamics, and function of proteins and other biomolecules (Ball, 2017). Water participates significantly during folding through hydrophobic interactions and mediates binding through the hydrogen bond in complex formation. Thermodynamic changes in the aqueous environment critically affect the stability of biomolecules. In spite of tremendous importance and intensive research for more than 50 years, the hydrophobic effect and its physical origin remains a matter of debate (Bagchi, 2013). Due to the intriguing nature of this phenomenon it is important to gain an understanding of the simple systems.


2) Dynamic mechanism of ligand protein binding.

The binding of ligands to specific protein sites (protein binding pockets) is used to switch proteins among states of different function. Therefore, the detailed physicochemical characterization of ligand-protein binding is crucial for the understanding of many biological processes occurring in living organisms including molecular recognition, signaling regulation, and enzymatic catalysis. It is also crucial for the development of target-based design and discovery of small-molecule drugs for the treatment of diseases. In general ligand-protein binding can occur through parallel mechanisms with varying aspects of induced-fit or conformational selection models (Greives, 2014).


3) Understanding intrinsically disordered proteins.

The investigation of the protein intrinsic disorder phenomenon has grown in recent years, with the increasing evidence of the significance of this class of proteins within the proteome. Since the identification of the first intrinsically disordered proteins (IDPs) at beginning in the ’90, the number of validated IDPs or proteins containing intrinsically protein disordered regions (IDPRs) has grown to more than a 1000 of proteins described in the literature (Uversky, 2017). The very existence of these proteins has challenged our understanding of protein structure and folding theories.


4) Transport mechanisms through membrane proteins.

Exchange of molecules across cellular membrane carried out by membrane proteins is one of the most essential biological processes in all living organisms. Membrane protein/transporters, in addition to their role as specific carriers for ions and small molecules, can also behave as water channels (Zeuthen 2010). However, neither the location of the water pathway in the protein nor their functional importance is known. Membrane transporters perform their function while intimately interacting with lipid molecules and water. Explicit representation of these molecular species in all-atom MD simulations enables us to closely probe many possible mechanisms by which they can affect transport function (Li 2015). The transport of membrane proteins involves highly diverse events of structural changes, ranging from local rearrangements at the binding sites and their gating elements, to global conformational transitions. Depending on the timescale of these events, their investigation may be covered with conventional MD simulations or require different methods of model simplifications or sampling enhancement.

5) Protein’s propensities to aggregate (formation of amyloids).

Protein self-assembling is an important generic mechanism that offers an unlimited source of varying properties and functions (Dobson, 2002). Moreover, misfolding and subsequent self-assembly of peptide and protein molecules into various aggregates is a common molecular mechanism of a number of lethal human diseases (Knowles, 2014). The mechanism of misfolding and aggregation of peptides and proteins is poorly understood. Reasons and initiators of conformational changes of peptides and proteins to form pathological aggregates in vivo are also unclear. Therefore, the understanding of the folding/misfolding mechanism, protein stability and structures of misfolded proteins and model fibrous proteins would significantly improve the current comprehension of these physiological processes.



Research concept with roles of laboratory members.



Bagchi B., Water in Biological and Chemical Processes, Cambridge UP, (2013).

Ball P., Proc. Natl. Acad. Sci. U. S. A., 114, 13327-13335 (2017).

Dobson C.M. , Nature, 418, 729-730 (2002).

Greives N., Zhou H.X., Proc. Natl. Acad. Sci. U. S. A., 111, 10197−10202 (2014).

Uversky V. N., Cell Mol Life Sci., 74, 3065-3067 (2017).

Zeuthen T, J. Membr. Biol 234, 57-73, (2010).

Li J., Wen P.-C., Moradi M., Tajkhorshid E, Curr. Op. Struct. Biol. 31, 96-105, (2015).

Knowles P.J.T, et. al., Nat. Rev. Mol. Cell Biol. 15, 384–396 (2014).


References of team members from research topics


Avbelj F., Proc. Natl. Acad. Sci. U. S. A., 108, 1794-1798 (2011).
Avbelj F., Golič Grdadolnik S., Grdadolnik J.,et al, PNAS. U.S.A.,103, 1272-1277 (2006).
Balog E., Perahia D., Smith J.C., Merzel F., J. Phys. Chem. B., 115, 6811-7 (2011).
Godec A., Smith J.C. and Merzel F., Phys. Rev. Lett. 107, 267801 (2011).
Godec A., Merzel F., J. Am. Chem. Soc. 134, 17574 (2012).
Godec, A., Smith, J.C. Merzel, F., Phys Rev Lett 111, 127801 (2013).
Grdadolnik J., Merzel F., Avbelj F., Proc. Natl. Acad. Sci. U. S. A. 114, 322 (2017).
Grdadolnik J., Mohaček-Grošev V., Baldwin R. L.,Avbelj F., PNAS. U. S. A., 108, 1794-1798 (2011)
Merzel F., Fontaine-Vive F., et al., J. Phys. Rev. E, 76, 031917-1-031917-5 (2007).
Mirtič A., Grdadolnik J., Biophys Chem., vol. 175-176, 47-53 (2013).
Mirtič A, Merzel F., Grdadolnik J., Biopolymers 101, 814-818 (2014).
Novak U., PhD Thesis, Josef Stefan post Graduate school, 2017
Novak U., Grdadolnik J., J. Mol. Struct., 1135, 138-143 (2017).
Paoletti F., et al., Biochem. Soc. Trans., 34, 605–606 (2006).
Paoletti F., et al.., Proteins, 75, 990–1009 (2009).
Paoletti F., et al.., PloS One, 6, e22615 (2011).
Simčič M., Kocjan D., Golič Grdadolnik, et al. S. J. Med. Chem., 52, 2899-908 (2009).
Simčič M., Golič Grdadolnik S., et al., PLoS One, 7(12), e52817 (2012).
Simčič M., Kocjan D., Golič Grdadolnik S., et al, Eur. J. Med. Chem., 83, 92-101 (2014).
van Eijck L, Merzel F, et al., 2011 107 088102, (2011).
Zidar J., Merzel F., J. Phys. Chem. B, vol. 115, 2075-2081 (2011).

color contrast
text size
highlighting content
zoom in