Wiesław Nowak

• prof. zw. dr hab.
• Professor (Full) at Nicolaus Copernicus University

Photoactive proteins absorb light and undergo structural changes that enable them to perform essential biological functions. These proteins are critical for understanding light-induced biological processes, making them important in biophysics, biotechnology, and medicine. One effective approach to uncovering photoactive processes is through computa...

Insecticides used in various formulations are inevitable in agricultural pest control and prevention of vector-borne diseases. Piperonyl butoxide (PBO) is a synergist widely used to enhance the effectiveness of insecticides, notably pyrethroids, by inhibiting the detoxifying cytochrome P450 enzymes, thus reducing the capacity of insects to metaboli...

l-Asparaginase (l-ASNase) catalyzes the hydrolysis of l-asparagine, leading to its depletion and subsequent effects on the cellular proliferation and survival. In contrast to normal cells, malignant cells that lack asparagine synthase are extremely susceptible to asparagine deficiency. l-ASNase has been successfully employed in treating pediatric l...

Atomic Force Microscopy (AFM) is a powerful but demanding imaging technique used also to study the interaction strength of single biomolecules by force spectroscopy. Here we provide a viAFM program designed to facilitate multi- directional steered molecular dynamics simulations and analysis of forces required to disrupt protein complexes thus mimic...

Glycine is considered to be crucial in the formation of proteins and prebiotic substances. Nevertheless, the mechanism of spontaneous glycine formation under prebiotic Earth conditions or within the interstellar medium (ISM) remains a topic of debate, given the changing geochemical environment over Earth’s history and the difficulty of detecting it...

Ferroptosis is a regulated form of cell death, the mechanism of which is still to be understood. 15-lipoxygenase (15LOX) complex with phosphatidylethanolamine (PE)-binding protein 1 (PEBP1) catalyzes the generation of pro-ferroptotic cell death signals, hydroperoxy-polyunsaturated PE. We focused on gaining new insights into the molecular basis of t...

Diseases spread by mosquitoes lead to the death of 700,000 people each year. The main way to reduce transmission is vector control by biting prevention with chemicals. However, the most commonly used insecticides lose efficacy due to the growing resistance. Voltage-gated sodium channels (VGSCs), membrane proteins responsible for the depolarizing ph...

Diseases spread by mosquitoes lead to death of 700,000 people each year. The main way to reduce transmission is vector control by biting prevention with chemicals. However, the most commonly used insecticides lose efficacy due to the growing resistance. Voltage-gated sodium channels (VGSCs), membrane proteins responsible for the depolarizing phase...

Commonly used techniques, such as CryoEM or X-ray, are not able to capture the structural reorganizations of disordered regions of proteins (IDR); therefore, it is difficult to assess their functions in proteins based exclusively on experiments. To fill this gap, we used computational molecular dynamics (MD) simulation methods to capture IDR dynami...

The purinergic signaling pathway is the oldest evolutionary transmitter system that regulates a wide array of physiological and pathophysiological processes in central nervous system. However, the question of how the purinergic compounds interact with administrated drugs is rarely addressed. We aimed to clarify the interplay between purinergic sign...

Insight into enthalpic and entropic contributions to the activation free energy of noncovalent bonds is crucial for understanding various phenomena in molecular systems, from formation of different molecular conformers to complex biophysical and biochemical processes. Standard experimental and computational methods provide only the average strength...

Commonly used techniques, such as CryoEM or Xray, are not able to capture the structural reorganizations of disordered regions of proteins (IDR), therefore it is difficult to assess their functions in proteins based exclusively on experiments. To fill this gap, we used computational molecular dynamics simulations methods to capture IDR dynamics and...

Insect vector-borne diseases pose serious health problems, so there is a high demand for efficient molecules that could reduce transmission. Using molecular docking and molecular dynamics (MD) simulation, we studied a series of compounds acting on human and insect muscarinic acetylcholine receptors (mAChRs), a novel target of synergistic agents in...

The ability of phytochromes to act as photoswitches in plants and microorganisms depends on interactions between a bilin-like chromophore and a host protein. The interconversion occurs between the spectrally distinct red (Pr) and far-red (Pfr) conformers. This conformational change is triggered by the photoisomerization of the chromophore D-ring py...

Petri nets (PNs) are bipartite graphs with two types of nodes: places and transitions. Places usually represent objects and transitions represent some actions or reactions. Places may contain tokens, which according to defined rules, can be transferred between places by transitions. The basic idea of PNs is simple. However, it allows to create a wi...

The ability of phytochromes to act as photoswitches in plants and microorganisms depends on interactions between a bilin-like chromophore and a protein. The interconversion occurs between the spectrally distinct red (Pr) and far-red (Pfr) conformers. This conformational change is triggered by the photoisomerization of the chromophore D-ring pyrrole...

The ability of phytochromes to act as photoswitches in plants and microorganisms depends on interactions between a bilin-like chromophore and a protein. The interconversion occurs between the spectrally distinct red (Pr) and far-red (Pfr) conformers. This conformational change is triggered by the photoisomerization of the chromophore D-ring pyrrole...

ATP-sensitive potassium (KATP) channels are present in numerous organs, including the heart, brain, and pancreas. Physiological opening and closing of KATPs present in pancreatic β-cells, in response to changes in the ATP/ADP concentration ratio, are correlated with insulin release into the bloodstream. Sulfonylurea drugs, commonly used in type 2 d...

Animal venoms are considered as a promising source of new drugs. Sea anemones release polypeptides that affect electrical activity of neurons of their prey. Voltage dependent sodium (Nav) channels are the common targets of Av1, Av2, and Av3 toxins from Anemonia viridis and CgNa from Condylactis gigantea. The toxins bind to the extracellular side of...

Inward rectifying potassium ion channels (KATP), sensitive to the ATP/ADP concentration ratio, play an important, control role in pancreatic beta cells. The channels close upon the increase of this ratio, which in turn, triggers insulin release to blood. Numerous mutations in KATP lead to severe and widespread medical conditions such as diabetes. T...

The insect repellent IR3535 is one of the important alternative in the fight against mosquito-borne disease such as malaria, dengue, chikungunya, yellow fever and Zika. Using a multidisciplinary approach, we propose the development of an innovative insecticide-based vector control strategy using an unexplored property of IR3535. We have demonstrate...

Detailed knowledge of intramolecular hydrogen bonds, including their nanomechanics, in a peptide secondary structure is crucial for understanding mechanisms of numerous biochemical processes. Single-molecule force spectroscopy has become a powerful tool to study directly the mechanical properties of single biopolymers and monitoring the hydrogen bo...

Reelin is a large glycoprotein controlling brain development and cell adhesion. It regulates the positioning of neurons, as well as neurotransmission and memory formation. Perturbations in reelin signaling are linked to psychiatric disorders. Reelin participates in signal transduction by binding to the lipoprotein receptors VLDLR and ApoER2 through...

The catalytic effects of complex minerals or meteorites are often mentioned as important factors for the origins of life. To assess the possible role of nanoconfinement within a catalyst consisting of montmorillonite (MMT) and the impact of local electric field on the formation efficiency of the simple hypothetical precursors of nucleic acid bases...

A method of purifying cyclododecyl 2,4-dihydroxybenzoate as a potential replacement template molecule for preparation of molecularly-imprinted polymers for isolation of zearalenone in urine was developed. Full physicochemical characteristics of cyclododecyl 2,4-dihydroxybenzoate for the first time included crystallographic analysis and molecular mo...

Mutations in gene KCNJ11 encoding the Kir6.2 subunit of the ATP-sensitive potassium channel (KATP), a representative of a quite complex biosystem, may affect insulin release from pancreatic beta-cells. Both gain and loss of channel activity are observed, which lead to varied clinical phenotypes ranging from neonatal diabetes to congenital hyperinsu...

Epidermolysis bullosa is a group of inherited blistering skin diseases resulting in most cases from missense mutations in KRT5 and KRT14 genes encoding the basal epidermal keratins 5 and 14. Here, we present a patient diagnosed with a localized subtype of epidermolysis bullosa simplex caused by a heterozygous mutation p.Ala428Asp in the KRT5 gene,...

The dissociation of huperzine A (hupA) from Torpedo californica acetylcholinesterase (TcAChE) was investigated by 4-microsecond unbiased and biased all-atom molecular dynamics (MD) simulations in explicit solvent. We performed our study using memetic sampling (MS) for the determination of reaction pathways (RPs), metadynamics to calculate free ener...

Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, without available antidotal therapy. Recently, a potential treatment for CO poisoning was introduced, based on binding of CO by neuroglobin (Ngb) with a mutated distal histidine (H64Q). Here, we present an atomistic mechanism of CO trapping by H64Q Ngb revealed by nonadiabatic m...

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Background Ichthyosis and neurological involvement occur in relatively few known Mendelian disorders caused by mutations in genes relevant both for epidermis and neural function. Objectives To identify the cause of a similar phenotype of ichthyotic keratoderma, spasticity, mild hypomyelination (on MRI) and dysmorphic features (IKSHD) observed in t...

Understanding the mechanisms of ligand binding to enzymes is of paramount importance for the design of new drugs. Here, we report on the use of a novel biased molecular dynamics (MD) methodology to study the mechanism of camphor binding to cytochrome P450cam. Microsecond-long MD simulations allowed us to observe reaction coordinates characterizing...

Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations i...

Computational simulations in biophysics describe the dynamics and functions of biological macromolecules at the atomic level. Among motions particularly important for life are the transport processes in heterogeneous media. The process of ligand diffusion inside proteins is an example of a complex rare event that can be modeled using molecular dyna...

Based on recent findings, there is growing evidence that many biological systems in the brain integrate biochemical information with mechanical signals making critical decisions about cell differentiation, synaptic regulation, axonal growth, neuronal migration or proliferation. These events seem to be controlled by the mechanical behavior of interv...

The present advanced state of the computer hardware offers superb opportunities for further explorations of protein structure and dynamics. Sound and well-established theoretical models are successfully used for searching new biochemical phenomena, correlations, and protein properties. In this chapter, the fast-growing field of computer simulations...

Excited-state molecular dynamics is a branch of theoretical physics and chemistry dedicated to simulating phenomena induced in molecules upon UV-visible light absorption. This includes the determination of nuclei positions evolution in time along with the calculation of electronic excited-states potential energy surfaces. This chapter presents both...

The protein structure refinement using conformational sampling is important in hitherto protein studies. In this paper we examined the protein structure refinement by means of potential energy minimization using immune computing as a method of sampling conformations. The method was tested on the x-ray structure and 30 decoys of the mutant of [Leu]E...

The presented results evidence that canine adipose-derived stem cells (ADSCs) represent the premature population of stem cells with great biological potential and properties. ADCS are easy to obtain and culture, able to differentiate into the neurogenic lineage as well as it is easy to control their proliferation rate with nucleotides and nucleosid...

In this work we propose an application of a nonlinear dimensionality reduction method to represent the high-dimensional configuration space of the ligand-protein dissociation process in a way facilitating interpretation. Rugged ligand expulsion paths are mapped into 2-dimensional space. The mapping retains main structural changes occurring during t...

Molecular dynamics (MD) simulation is a popular method of protein and nucleic acids research. Current MD output trajectories are huge �les and therefore they are hard to analyze. Petri nets (PNs) is a mathematical modeling language that allows for concise, graphical representation of complex data. We have developed a few algorithms for PNs generati...

The brain activity is to a large extent determined by states of neural cortex microcircuits. Unfortunately, accuracy of results from neural circuits' mathematical models is often biased by the presence of uncertainties in underlying experimental data. Moreover, due to problems with uncertainties identification in a multidimensional parameters space...

This work examines the impact of energy over-minimization on an ensemble of biological molecules subjected to the potential energy minimization procedure in vacuum. In the studied structures, long potential energy minimization stage leads to an increase of the main- and side-chain entropies in proteins. We show that such over-minimization may diver...

Ligand diffusion through a protein interior is a fundamental process governing biological signaling and enzymatic catalysis. A complex topology of channels in proteins leads often to difficulties in modeling ligand escape pathways by classical molecular dynamics simulations. In this paper two novel memetic methods for searching the exit paths and c...

Proliferating Cell Nuclear Antigen (PCNA) is a homotrimeric DNA sliding clamp involved in DNA replication, repair and cell cycle control. Understanding determinants of mechanical stability of a PCNA monomer composed of two N- and C-terminal domains requires all-atom and coarse-grained steered molecular dynamics simulations. Three schemes of unfoldi...

The first experiment showing the effects of specific interaction forces using lateral force microscopy (LFM) was demonstrated for lectin-carbohydrate interactions some years ago. Such measurements are possible under the assumption that specific forces strongly dominate over the non-specific ones. However, obtaining quantitative results requires the...

Insect vector-borne diseases remain one of the principal causes of human mortality. In addition to conventional measures of insect control, repellents continue to be the mainstay for personal protection. Because of the increasing pyrethroid-resistant mosquito populations, alternative strategies to reconstitute pyrethroid repellency and knock-down e...

Mesenchymal stem cells (Msc) differentiate typically to chondrocytes. In our lab we have created neuronal-like cells from Msc. In this presentation results of atomic force microscopy (AFM) measurements of mechanical properties such as Young modulus or friction during this differentiation will be reported. Differentiations leads to noticeable change...

Excited-state molecular dynamics is a branch of theoretical physics and chemistry dedicated to simulating phenomena induced in molecules upon UV-visible light absorption. This includes the determination of nuclei positions evolution in time along with the calculation of electronic excited-states potential energy surfaces. This chapter presents both...

Amyloidosis, a serious and widespread disease with a genetic background, manifests itself through the formation of dangerous fibrils in various organs. Apart from the polluted environment and an unhealthy lifestyle, genetic factors may accelerate this process leading in some cases to lethal damages to the body. Recently, a growing interest in amylo...

We report the discovery of a new mechanical transition in stretched and topologically constrained DNA. We used a well established technique of stretching single molecules with an untreated Atomic Force Microscope tip to extend DNA. We explored the DNA mechanics under previously untested high stretching force regime, up to 1.8 nN of possible limit o...

The mechanism of FN(III)9 fibronectin domain adsorption at pH7 onto various and contrasting model surfaces has been studied using atomistic molecular dynamics (MD) simulations. We use an ionic model to mimic mica surface charge density, but without a long-range electric field above the surface; a silica model with a long-range electric field simila...

About 75% of cases of epidermolysis bullosa simplex result from mutations in KRT5 and KRT14 genes. Here, we report a family with a novel heterozygous missense mutation p.Leu418Gln in the KRT14 gene causing EBS of phenotype varying from EBS-loc to EBS-gen intermed. To the best of our knowledge, the family reported by us is the largest one in whom tw...

Absorption and fluorescence properties, excited state lifetimes and fluorescence quantum yields were determined for a series of 3,5-diarylaminobenzene derivatives in solvents of different polarities. The role of the nitrile, methyl, phenyl and naphthyl substituents is discussed. Especially the steric effects on the spectroscopic behaviour of the in...

Computer simulations of protein unfolding substantially help to interpret force-extension curves measured in single-molecule atomic force microscope (AFM) experiments. Standard all-atom (AA) molecular dynamics simulations (MD) give a good qualitative mechanical unfolding picture but predict values too large for the maximum AFM forces with the commo...

We show results of our high force (up to 1.8 nN) atomic force microscopy force spectroscopy measurements of a double stranded DNA. We have found that the force spectra of torsionally constrained molecules display a small plateau occurring at a force of approximately 1 nN. This transition is absent in molecules with rotational freedom. Based on all-...

Aging society faces the problem of deterioration of lifes' quality. Thus the research targeted on improvement of humans health is important and challenging task. The senile systematic amyloidosis, disease that is caused by unnaturally forming fibrils, affects about 25% of population over 80th year of life and may be lethal. One of proteins involve...

Monocyte-chemoattractant protein-1 (MCP-1), also known as CCL2, is a potent chemoattractant of T cells and monocytes, involved in inflammatory and angio-proliferative brain and retinal diseases. Higher expression of MCP-1 is observed in metastatic tumors. Unusual levels of MCP-1 in the brain may be correlated with autism. Immunochemistry where atom...

Abstract: Vector Borne Diseases (VBD) present a serious threat to millions of people. In this paper various computational approaches towards new drugs design against some of them are reviewed. Malaria attracts particular attention of computational medicinal chemists. A promising strategy of the fight with VBD is usage of insect repellents. N,N-Diet...

We introduce spectral density distribution moments as molecular descriptors. We demonstrate that these descriptors correctly represent the molecular structure. To prove the correctness of the new descriptors, we consider the IR spectra of 76 chloronaphthalenes. We show that the consecutive substitutions of the hydrogen atoms by the chlorine atoms a...

Nanostructures created by living organisms, optimized through millions of years of evolution, can be a valuable inspiration for nanotechnology. We employ atomic force microscopy to examine such structures in materials created by common organisms caddisy and diatoms. Caddisy larvae are well known for their ability to spin silk, which serves as an ad...

Algorithms based on graphs and networks offer great potential for modeling of physiological processes. In this paper bipartite graphs called Petri Nets (PN) are presented and their utility in modeling of the immune system is highlighted. We present our improved PN model of the immune system. The coupling between fever and autism is studied using th...

Hybrid nanostructures are often composed of inorganic parts and "biological" ones. Optimized through million years of evolution light harvesting proteins are hard to mimic synthetically. Promising strategy in search for efficient solar cells is an attachment of selected natural protein systems to inorganic quantum dots. Such experimental hybrid str...

Every year the prevalence of Autism Spectrum of Disorders (ASD) is rising. Is there a unifying mechanism of various ASD cases at the genetic, molecular, cellular or systems level? The hypothesis advanced in this paper is focused on neural dysfunctions that lead to problems with attention in autistic people. Simulations of attractor neural networks...

Neurexins are proteins involved in synapse signaling. Understanding molecular recognition in neurons requires a knowledge of neurexin elasticity at a single molecule level. We apply, for the first time, AFM force spectroscopy to reveal mechanical properties of rat neurexin 1α (NRXN1α). Spectra indicate a flexible hinge. The first event in the unfol...

Advances in computer technology offer great opportunities for new explorations of protein structure and dynamics. Sound and well-established theoretical models may be successfully used for searching new biochemical phenomena, correlations, and protein properties. In this review the fast-growing field of computer simulations of protein dynamics is p...

Frequency of diagnoses of diseases, which belong to Autism Spectrum of Disorders (ASD) increases with each year. The question is: is there a unifying mechanism at molecular, cellular or systems level? In the paper we present our point of view to problem of attention in autistic people. Simulations using neural network model with attractor analysis...

Contactins are modular extracellular cell matrix proteins that are present in the brain, and they are responsible for the proper development and functioning of neurons. They contain six immunoglobulin-like IgC2 domains and four fibronectin type III repeats. The interactions of contactin with other proteins are poorly understood. The mechanical prop...

Caddisfly (Trichopera) can glue diverse material underwater with a silk fiber. This makes it a particularly interesting subject for biomimetcs. Better understanding of silk composition and structure could lead to an adhesive capable to close bleeding wounds or to new biomaterials. However, while spiderweb or silkworm secretion is well researched, c...

A recent survey of 17 134 proteins has identified a new class of proteins which are expected to yield stretching induced force peaks in the range of 1 nN. Such high force peaks should be due to forcing of a slip-loop through a cystine ring, i.e., by generating a cystine slipknot. The survey has been performed in a simple coarse grained model. Here,...

We use a single molecule atomic force spectroscopy combined with the steered molecular dynamics simulation to determine a mechanical behavior of neural cell adhesion protein contactin during its unfolding. Force curves typical for modular proteins were observed, showing at most four unfolding peaks. The analysis of force spectra performed within wo...

A traditional photonic-force microscope (PFM) results in huge sets of data, which requires tedious numerical analysis. In this paper, we propose instead an analog signal processor to attain real-time capabilities while retaining the richness of the traditional PFM data. Our system is devoted to intracellular measurements and is fully interactive th...

a b s t r a c t Nitrile hydratase (NHase), an important biotechnological enzyme, has been investigated using a steered molecular dynamics computer modelling for the first time. An external force applied to the docked ligands was used to determine transport paths for acrylonitrile (substrate) and acrylamide (product). The average drag force of 120 p...

The physiological role of recently discovered human neuroglobin (Ngb) is still unknown. Sound hypothesis says that it protects brain during hypoxia. In this paper the advanced potential of mean force by implicit ligand sampling (PMF/ILS) method is used to study the free energy landscape of Ngb for O(2), NO and CO ligands. The multiple diffusion pat...

Nitrile hydratase (NHase) is an enzyme used in the industrial biotechnological production of acrylamide. The active site, which contains nonheme iron or noncorrin cobalt, is buried in the protein core at the interface of two domains, alpha and beta. Hydrogen bonds between betaArg-56 and alphaCys-114 sulfenic acid (alphaCEA114) are important to main...

This paper aims at an application of the statistical theory of spectra to the classification of chemical compounds. It has been shown that the moments of the intensity distributions may be used as molecular descriptors. The new descriptors have been tested using spectra of nitriles and amides. The dependence of the accuracy of the classification on...

Nitrile hydratase (NHase) is a metalloenzyme used in industrial biotechnology for a large scale production of common chemicals. NHases convert nitriles to the corresponding amides. Although the structures of some forms of NHases containing nonheme low spin Fe(III) or low spin noncorrinoid Co(III) are known, neither a catalytic mechanism nor the rea...

Thiocyanate hydrolase (SCNase, pdb code 2DD5) is a novel metaloenzyme containing non- corrinoid Co3+ in the active site. Despite identical structure of the activ e sites, high sequence and structural similarity of SCNase and nitrile hydratases (NHases) both enzymes catalyse dif- ferent reactions. The SCNase enzyme catalyses the degradation of thioc...

The monomeric, intracellular hemoglobin from the fruit fly D rosophila Melanogaster (DmHb) has been discovered in 2005. It came out that the oxygen supply system in insects is more com- plex then previously thought. Details on diffusion of gases, ligands discrimination and hexa- to pentacoordination changes remain unclear. Here we present the resul...

Multi-dimensional aspects of similarity studies of DNA/RNA sequences are emphasized. The new graphical representation presented in our recent papers and its descriptors are used as numerical examples of the multi-dimensionality.

We propose the statistical moments of mass-density distributions (created for two orthogonal directions) as new descriptors of DNA sequences. The distributions are derived using a 2D-dynamic representation technique proposed in our previous paper in which the sequence is coded by a set of point masses properly distributed in 2D-space.

Cytoglobin (Cyg)--a new member of the vertebrate heme globin family--is expressed in many tissues of the human body but its physiological role is still unclear. It may deliver oxygen under hypoxia, serve as a scavenger of reactive species or be involved in collagen synthesis. This protein is usually six-coordinated and binds oxygen by a displacemen...

Nitrile hydratase (NHase) is an enzyme containing non-corrin Co3+ in the non-standard active site. NHases from Pseudonocardia thermophila JCM 3095 catalyse hydration of nitriles to corresponding amides. The efficiency of the enzyme is 100 times higher for aliphatic nitriles then aromatic ones. In order to understand better this selectivity dockings...

A new 'dynamic' 2D-graphical representation of DNA sequences is presented. The model is based on 2D-plots that have been used before and are easy to visualize, but it removes many degeneracies present in the previous approaches. The moments of inertia of the 'dynamic' graphs are proposed as a new kind of descriptor for DNA sequences.