Publications
Proton translocation through lipid membranes is a fundamental process in the field of biology. Several theoretical models have been developed and presented over the years to explain the phenomenon, yet the exact mechanism is still not well understood. Here, we show that …
Journal of the American Chemical Society, 2024
SHP2 is a tyrosine phosphatase that plays a regulatory role in multiple intracellular signaling cascades and is known to be oncogenic in certain contexts. In the absence of effectors, SHP2 adopts an autoinhibited conformation with its N-SH2 domain blocking the active …
Computational and Structural Biotechnology Journal, 2024
Molecular Simulations of Liquid Jet Explosions and Shock Waves Induced by X-Ray Free-Electron Lasers
X-ray free-electron lasers (XFELs) produce x-ray pulses with high brilliance and short pulse duration. These properties enable structural investigations of biomolecular nanocrystals, and they allow one to resolve the dynamics of biomolecules down to the femtosecond …
Physical Review Letters, 2023
Src-homology 2 (SH2) domains are protein interaction domains that bind to specific peptide motifs containing phosphotyrosine. SHP2, a tyrosine phosphatase encoded by PTPN11 gene, which has been emerged as positive or negative modulator in multiple signaling pathways, …
Methods in Molecular Biology, 2023
The emergence of multidrug-resistant pathogens led to a critical need for new antibiotics. A key property of effective antibiotics against Gram-negative bacteria is their ability to permeate through the bacterial outer membrane via transmembrane porin proteins. …
Journal of Chemical Information and Modeling, 2023
Resolving the structural dynamics of bond breaking, bond formation, and solvation is required for a deeper understanding of solution-phase chemical reactions. In this work, we investigate the photodissociation of triiodide in four solvents using femtosecond …
Journal of the American Chemical Society, 2023
Electric fields across lipid membranes play important roles in physiology, medicine, and biotechnology, rationalizing the wide interest in modeling transmembrane potentials in molecular dynamics simulations. Transmembrane potentials have been implemented with external …
Journal of Chemical Theory and Computation, 2023
Molecular dynamics simulations have been widely used to study solute permeation across biological membranes. The potential of mean force (PMF) for solute permeation is typically computed using enhanced sampling techniques such as umbrella sampling (US). For bulky …
Journal of Chemical Theory and Computation, 2023
Unassisted ion transport through lipid membranes plays a crucial role in many cell functions without which life would not be possible, yet the precise mechanism behind the process remains unknown due to its molecular complexity. Here, we demonstrate a direct link …
Journal of the American Chemical Society, 2022
Staphylococcus epidermidis is a commensal bacterium on human skin that is also the leading cause of medical device-related infections. The accumulation-associated protein (Aap) from S. epidermidis is a critical factor for infection via its ability to mediate biofilm …
Journal of Molecular Biology, 2022
Atmospheric aerosols contain organic molecules that serve as cloud condensation nucleation sites and affect the climate. Several experimental and simulation studies have been dedicated to investigate their surface propensity, but the mechanisms that drive them to the …
Physical Chemistry Chemical Physics, 2021
The Src-homology-2 domain–containing phosphatase SHP2 is a critical regulator of signal transduction, being implicated in cell growth and differentiation. Activating mutations cause developmental disorders and act as oncogenic drivers in hematologic cancers. SHP2 is …
Proceedings of the National Academy of Sciences, 2021
Noncoding intron sequences present in precursor mRNAs need to be removed prior to translation, and they are excised via the spliceosome, a multimegadalton molecular machine composed of numerous protein and RNA components. The DEAH-box ATPase Prp2 plays a crucial role …
Acta Crystallographica Section D, 2021
Arginine (R)-rich peptides constitute the most relevant class of cell-penetrating peptides and other membrane-active peptides that can translocate across the cell membrane or generate defects in lipid bilayers such as water-filled pores. The mode of action of R-rich …
European Biophysics Journal, 2021
Small- and wide-angle X-ray scattering (SAXS/WAXS/SWAXS) have evolved to be accurate tools used to gain structural information of biomolecules in solution. However, the interpretation of SWAXS data remains challenging owing to the low information content of the data and …
Methods in Molecular Biology, 2021
Topological transitions of membranes, such as pore formation or membrane fusion, play key roles in biology, biotechnology, and in medical applications. Calculating the related free-energy landscapes has been complicated by the fact that such processes involve a sequence …
Journal of Chemical Theory and Computation, 2021
Itraconazole is a triazole drug widely used in the treatment of fungal infections, and it is in clinical trials for treatment of several cancers. However, the drug suffers from poor solubility, while experiments have shown that itraconazole delivery in liposome …
The Journal of Physical Chemistry B, 2020
SH2 domain-containing tyrosine phosphatase 2 (SHP2), encoded by PTPN11, plays a fundamental role in the modulation of several signaling pathways. Germline and somatic mutations in PTPN11 are associated with different rare diseases and hematologic malignancies, and …
Journal of Chemical Information and Modeling, 2020
The interactions between proteins and membranes play critical roles in signal transduction, cell motility, and transport, and they are involved in many types of diseases. Molecular dynamics (MD) simulations have greatly contributed to our understanding of …
Progress in Molecular Biology and Translational Science, 2020
Small-angle X-ray scattering (SAXS) is a widely used experimental technique, providing structural and dynamic insight into soft-matter complexes and biomolecules under near-native conditions. However, interpreting the one-dimensional scattering profiles in terms of …
The Journal of Physical Chemistry Letters, 2020
Intrinsically disordered proteins (IDPs) play key roles in biology and disease, rationalizing the wide interest in deriving accurate solution ensembles of IDPs. Molecular dynamics (MD) simulations of IDPs often suffer from force-field inaccuracies, suggesting that …
Journal of Chemical Theory and Computation, 2019
Small-angle X-ray and small-angle neutron scattering (SAXS/SANS) provide unique structural information on biomolecules and their complexes in solution. SANS may provide multiple independent data sets by means of contrast variation experiments, that is, by measuring at …
Journal of Chemical Theory and Computation, 2019
Steroid flares are common side effects associated with corticosteroid treatment, and have been recently theorized to be a consequence of drug crystallization. It was previously reported that the lipid bilayer can promote crystallization of cortisone at high local …
Chemistry and Physics of Lipids, 2019
Polycations are an attractive class of macromolecules with promising applications as drug/gene carriers and biocides. The chemical structure and concentration of a polycation determine its interaction with cellular membranes and, hence, are crucial parameters for …
ACS Biomaterials Science & Engineering, 2018
Small-angle X-ray scattering (SAXS) is a popular experimental technique used to obtain structural information on biomolecules in solution. SAXS is sensitive to the overall electron density contrast between the biomolecule and the buffer, including contrast contributions …
Physical Chemistry Chemical Physics, 2018
In-solution small-angle X-ray and neutron scattering (SAXS/SANS) have become popular methods to characterize the structure of membrane proteins, solubilized by either detergents or nanodiscs. SANS studies of protein-detergent complexes usually require deuterium-labeled …
The Journal of Physical Chemistry Letters, 2018
Abstract Surfactants have found a wide range of industrial and scientific applications. In particular, detergent micelles are used as lipid membrane mimics to solubilize membrane proteins for functional and structural characterization. However, an atomic-level …
Angewandte Chemie International Edition, 2018
Small-angle and wide-angle X-ray scattering in solution (SAXS, WAXS, SWAXS) is an increasingly accurate method for obtaining information on biomolecular structures, ensembles, and time-resolved dynamics at near-native conditions. However, the interpretation of the …
Current Opinion in Structural Biology, 2017
Various biophysical processes involve the formation of aqueous pores over lipid membranes, including processes of membrane fusion, antimicrobial peptide activity, lipid flip-flop, and membrane permeation. Reliable and efficient free-energy calculations of pore formation …
Journal of Chemical Theory and Computation, 2017
Membrane channels facilitate the efficient and selective flux of various solutes across biological membranes. A common approach to investigate the selectivity of a channel has been the calculation of potentials of mean force (PMFs) for solute permeation across the pore. …
The Journal of Physical Chemistry B, 2017
Molecular dynamics simulations are capable of predicting the permeability of lipid membranes for drug-like solutes, but the calculations have remained prohibitively expensive for high-throughput studies. Here, we analyze simple measures for accelerating potential of …
The Journal of Chemical Physics, 2016
“Protein quake” denotes the dissipation of excess energy across a protein, in response to a local perturbation such as the breaking of a chemical bond or the absorption of a photon. Femtosecond time-resolved small- and wide-angle X-ray scattering (TR-SWAXS) is capable …
Proceedings of the National Academy of Sciences, 2016
Transmembrane pores play an important role in various biophysical processes such as membrane permeation, membrane fusion, and antimicrobial peptide activity. In principal, all-atom molecular dynamics (MD) simulations provide an accurate model of pore formation in lipid …
Journal of Chemical Theory and Computation, 2016
In experimental studies of solubilized membrane proteins, the detergent corona influences the protein behavior and the resulting measurement. Thus, combinations of experimental techniques with atomistic modeling have been used to resolve corona structural parameters and …
The Journal of Physical Chemistry Letters, 2015
Lateral inhomogeneity plays a critical role for many properties of cholesterol-containing membranes, yet the thermodynamic forces involved in inhomogeneity remain poorly understood. Based on coarse-grained simulations of cholesterol in four increasingly unsaturated …
The Journal of Physical Chemistry Letters, 2015
Time-resolved wide-angle X-ray scattering (TR-WAXS) is an emerging experimental technique used to track chemical reactions and conformational transitions of proteins in real time. Thanks to increased time resolution of the method, anisotropic TR-WAXS patterns were …
The Journal of Chemical Physics, 2015
Validating Solution Ensembles from Molecular Dynamics Simulation by Wide-Angle X-ray Scattering Data
Wide-angle x-ray scattering (WAXS) experiments of biomolecules in solution have become increasingly popular because of technical advances in light sources and detectors. However, the structural interpretation of WAXS profiles is problematic, partly because accurate …
Biophysical Journal, 2014
Protein–gas interactions are important in biology. The enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes two competing reactions involving CO$_2$ and O$_2$ as substrates. Carboxylation of the common substrate ribulose-1,5-bisphosphate leads to …
Journal of the American Chemical Society, 2014
Ewald summation, which has become the de facto standard for computing electrostatic interactions in biomolecular simulations, formally requires that the simulation box is neutral. For non-neutral systems, the Ewald algorithm implicitly introduces a uniform background …
Journal of Chemical Theory and Computation, 2013
The solubility of organic molecules is a well established property, founded on decades of measurements, the results of which have been tabulated in handbooks. Under atmospheric conditions water droplets may form containing small amounts of other molecules. Such droplets …
Physical Chemistry Chemical Physics, 2012
Cholesterol plays an important role in maintaining the correct fluidity and rigidity of the plasma membrane of all animal cells, and hence, it is present in concentrations ranging from 20 to 50 mol %. Whereas the effect of cholesterol on such mechanical properties has …
Journal of the American Chemical Society, 2012
The chemical composition of small organic molecules is often very similar to amino acid side chains or the bases in nucleic acids, and hence there is no a priori reason why a molecular mechanics force field could not describe both organic liquids and biomolecules with a …
Journal of Chemical Theory and Computation, 2011
The Journal of Physical Chemistry B, 2011
Water is a demanding partner. It strongly attracts ions, yet some halide anions—chloride, bromide, and iodide—are expelled to the air/water interface. This has important implications for chemistry in the atmosphere, including the ozone cycle. We present a quantitative …
Proceedings of the National Academy of Sciences, 2011
The Weighted Histogram Analysis Method (WHAM) is a standard technique used to compute potentials of mean force (PMFs) from a set of umbrella sampling simulations. Here, we present a new WHAM implementation, termed g_wham, which is distributed freely with the GROMACS …
Journal of Chemical Theory and Computation, 2010
As a member of the ubiquitous ammonium transporter/methylamine permease/Rhesus (Amt/MEP/Rh) family of membrane protein channels, the 50 kDa Rhesus channel (Rh50) has been implicated in ammonia (NH$_3$) and, more recently, also in carbon dioxide (CO$_2$) transport. Here …
Journal of the American Chemical Society, 2010
The aquaglyceroporin from Plasmodium falciparum (PfAQP) is a potential drug target for the treatment of malaria. It efficiently conducts water and other small solutes, and is proposed to intervene in several crucial physiological processes during the parasitic life …
Physical Chemistry Chemical Physics, 2010
We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(β)146, and they sum up to a total …
PLOS Computational Biology, 2010
Aquaporins (AQPs) are a family of integral membrane proteins, which facilitate the rapid and yet highly selective flux of water and other small solutes across biological membranes. Molecular dynamics (MD) simulations contributed substantially to the understanding of the …
Handbook of Experimental Pharmacology, Aquaporins, 2008
Biomolecular processes are governed by free energy changes and thus depend on a fine-tuned interplay between entropy and enthalpy. To calculate accurate values for entropies from simulations is particularly challenging for the solvation shell of proteins, which …
Computer Physics Communications, 2008
Aquaporins and aquaglyceroporins form a family of pore proteins that facilitate the efficient and selective flux of small solutes across biological membranes. We studied the selectivity of aquaporin-1 (AQP1) and the bacterial glycerol facilitator, GlpF, for O$_2$, …
Proceedings of the National Academy of Sciences, 2008
Excessive water uptake through aquaporins can be life threatening, and disregulation of water permeability causes many diseases. Therefore, reversible aquaporin inhibitors are highly desired. In this paper, we identified the binding site for tetraethylammonium (TEA) of …
Pflügers Archiv - European Journal of Physiology, 2008
Quantum Monte Carlo simulations are used to study the dynamics and the critical properties of strongly correlated systems relevant to the fields of cold quantum gasses and high-Tc superconductivity. Recent advances in cooling techniques of quantum gasses allow to reach …
High Performance Computing in Science and Engineering' 04, 2004
